Energetics of Insect Diapause

EN56CH06-Hahn ARI 14 October 2010 10:28

Energetics of Insect DiapauseDaniel A. Hahn1 and David L. Denlinger2

1Department of Entomology and Nematology, University of Florida, Gainesville,Florida 32611; email: [email protected] of Entomology and Evolution, Ecology, and Organismal Biology, Ohio StateUniversity, Columbus, Ohio 43210; email: [email protected]

Annu. Rev. Entomol. 2011. 56:103–21

First published online as a Review in Advance onAugust 2, 2010

The Annual Review of Entomology is online atento.annualreviews.org

This article’s doi:10.1146/annurev-ento-112408-085436

Copyright c© 2011 by Annual Reviews.All rights reserved

0066-4170/11/0107-0103$20.00

Key Words

dormancy, metabolic depression, energy reserves, nutrienthomeostasis, costs of diapause, global warming

Abstract

Managing metabolic resources is critical for insects during diapausewhen food sources are limited or unavailable. Insects accumulate re-serves prior to diapause, and metabolic depression during diapause pro-motes reserve conservation. Sufficient reserves must be sequestered toboth survive the diapause period and enable postdiapause developmentthat may involve metabolically expensive functions such as metamor-phosis or long-distance flight. Nutrient utilization during diapause is adynamic process, and insects appear capable of sensing their energy re-serves and using this information to regulate whether to enter diapauseand how long to remain in diapause. Overwintering insects on a tightenergy budget are likely to be especially vulnerable to increased temper-atures associated with climate change. Molecular mechanisms involvedin diapause nutrient regulation remain poorly known, but insulin sig-naling is likely a major player. We also discuss other possible candidatesfor diapause-associated nutrient regulation including adipokinetic hor-mone, neuropeptide F, the cGMP-kinase For, and AMPK.

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Diapause: anenvironmentallypreprogrammedperiod of arresteddevelopment,characterized bymetabolic depressionthat can occur duringany stage of insectdevelopment

Photoperiodiccontrol of diapause:a response such asdiapause that is evokedin response topredictable, seasonalchanges in daylength

INTRODUCTION

Surviving long periods without eating is a chal-lenge, and this is precisely the challenge mostdiapausing insects confront. Diapause offersa tremendous adaptive advantage by allowingsurvival in seasonal environments that couldnot otherwise be tolerated and permits life cy-cle synchronization with periods suitable forgrowth, development, and reproduction. But tosucceed in this venture implies an impressive ca-pacity for managing energy reserves. Arrests of9–10 months are common and in a few casesdiapause may stretch to several years. What re-sources are sequestered? How are they parsedout during diapause, preserving enough nutri-ents to complete postdiapause challenges suchas metamorphosis and flight, energy-intensiveactivities that are frequent prerequisites beforefeeding can replenish lost reserves?

Insects use two strategies to mitigate the en-ergetic costs of diapause: accumulation of re-serves and metabolic depression. How does aninsect know when it has stored adequate re-serves? Do diapausing insects have an energy-sensing mechanism that signals depletion of acritical mass of reserves? Is metabolic depres-sion a simple turning down of the metabolicfurnace? We argue that diapause is a metaboli-cally dynamic state that may involve shifts fromone energy source to another as diapause pro-gresses, and in some cases diapause is charac-terized by dramatic pulses of metabolic activitythat spike with a frequency of several days. Weare just beginning to understand mechanismsregulating such decisions and processes in in-sects, and the goal of this review is to providethe basis for what we think are critical questionsfor understanding how resources are managedduring the extreme energy deprivation thatcharacterizes diapause.

Previous reviews provide a good contextfor understanding the ecological implicationsof insect diapause (26, 69, 107), photoperiodiccontrol of diapause (78, 92), hormonal (30)and molecular regulation of diapause (36),dynamics of the diapause state (64), and nutri-ent storage and utilization (48). Although our

previous review (48) is closely related to theissues presented here, the earlier paper placedmore emphasis on the ecological contextof nutrient issues associated with diapause,and this review focuses more extensively onphysiological mechanisms governing diapauseenergetics. We also recommend several re-views on the insect fat body and energetichomeostasis as background (5, 45, 102, 103).

CONSEQUENCES OF ENERGYSHORTFALLS AND ABUNDANCE

The energy reserves an insect sequesters can af-fect the decision to enter diapause, the decisionto terminate diapause, and fitness during thepostdiapause period. We discussed these impli-cations more fully in our earlier review (48) andonly briefly summarize this literature by citinga few recent papers.

Insects that have not sequestered sufficientreserves to survive a lengthy diapause have fouroptions: die during diapause or postdiapausedevelopment when all reserves have been de-pleted; opt to avert diapause, gambling that anattempt to produce one more generation is abetter option than dying; terminate diapauseprematurely when energy reserves become dan-gerously low; or compensate for this deficiencyby feeding during diapause. All four of these re-sponses do occur. Diapausing insects with lowenergy reserves do indeed have higher mortal-ity during diapause, as reported in numerousarthropods (48). The blow fly Calliphora vic-ina is a species capable of averting diapause ifit is too small: Undersized larvae, although ex-posed to diapause-inducing conditions of shortdaylength and low temperature, fail to enter di-apause if they are below a certain size (90). Thethird option, breaking diapause early, is also ev-ident in the larval diapause of C. vicina; under-sized larvae that do enter diapause terminatediapause much earlier than heavier larvae (90).The final option is available only to insects thatretain the ability to feed during larval or adultdiapause. Overwintering larvae of the damselflyLestes eurinus that enter winter with poor energy

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Juvenile hormone( JH): a family ofsesquiterpenoidsproduced by thecorpora allata ofinsects that acttogether withecdysteroids toregulate insectmolting,metamorphosis, andreproduction

Triacylglyceride: thedominant storage formof lipids in insectssynthesized and storedprimarily in the fatbody

reserves compensate by feeding more than theirwell-fed cohorts (28).

Extra reserves that remain with an insectafter diapause termination can be an asset forpostdiapause development and reproduction,enhancing postdiapause performance. Lipidreserves remaining after termination of adultreproductive diapause in the mosquito Culexpipiens are readily used for subsequent egg pro-duction (120). Diapause-destined larvae of thecorn stalk borer, Sesamia nonagrioides, feed morethan nondiapausing larvae, resulting in largeradults that produce more eggs (38). Similarly,seasonal field trapping data of bivoltine mothsin Estonia show that adults derived from pu-pae or larvae that overwintered in diapause werelarger than adults from subsequent nondiapausegenerations, despite lower host plant quality(108). However, gathering additional reservesneeded to ensure a successful diapause in itselfcan exact a toll. More time spent feeding canmake an insect more vulnerable to predationand parasitism, and as demonstrated in the but-terfly Aglais urticae, the added weight acquiredby feeding in preparation for winter can impairthe butterfly’s escape ability by decreasing itsflight muscle ratio, i.e., the ratio of thorax mus-cle mass to total body mass (3).

Although we usually think of the diapauseprogram driving the accumulation of energystores, the reverse is also possible, as seen inPolistes paper wasps (55). In this scenario, it isproposed that accumulation of hexameric stor-age proteins leads to suppression of juvenilehormone ( JH) production, a prerequisite for di-apause. Wasps that accumulate an abundance ofhexamerins thus produce less JH and are chan-neled into diapause, suggesting an evolutionaryintegration of nutritional and endocrine mech-anisms in diapause.

NUTRIENT STORAGE INPREPARATION FOR DIAPAUSE

Both diapausing and nondiapausing in-sects store metabolic reserves of the samethree macronutrient groups: lipids, carbohy-drates, and amino acids, as well as essential

micronutrients such as vitamins and minerals.Alterations in both the quantity and quality ofnutrient stores are often apparent in diapause-destined individuals. During diapause, reservesare used in cellular maintenance for bothcatabolic energy production and anabolicprocesses, including protein turnover andcell membrane maintenance and remodeling.Diapausing insects are simply not runningslower than nondiapausing insects of the samelife stage; they have entered an alternativedevelopmental pathway that has its ownmetabolic demands (64). For example, dia-pausing flesh fly pupae enhance cold hardinessby upregulating production of glycerol andseveral classes of heat shock proteins as acomponent of the diapause program. Thus,diapausing pupae require substantial quantitiesof amino acids and carbohydrate precursors tosupport synthesis of these protective molecules(33).

Because of their high caloric content, lowhydration state, and perhaps relatively highyield of metabolic water, triacylglyceride fatstores are the most important energy reservein most diapausing insects, often accountingfor as much as 80–95% of total lipid content.The fat body is the primary site of fatty acidsynthesis, triacylglyceride production, and tri-acylglyceride storage in insects, although allcells can store some triacylglycerides and sub-stantial stores can occur in tissues such as thelarge, metabolically active flight muscles (118).Diapause-destined individuals of some speciesaccumulate greater triacylglyceride stores thannondiapausing individuals, and increased tria-cylglyceride storage is thought to be an impor-tant factor mitigating the metabolic demands ofdiapause (26, 48, 107). To accumulate greaterreserves, diapausing individuals must eat more,increase their digestive efficiency, divert nu-trients away from somatic growth to storage,or use a combination of these, nominating theprediapause preparatory period as an excel-lent developmental window for examining theregulation of feeding and nutrient processing.Although the dogma is that diapause-destinedinsects accumulate greater reserves, this is not

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always the case (48). What ecological and physi-ological factors determine whether a species ac-cumulates greater reserves as part of its diapausepreparatory program is a wide-open question.

The fatty acid composition of triacylglyc-erides accumulated prior to diapause can dif-fer qualitatively and quantitatively betweennondiapause and diapause-destined individu-als within a species. Fatty acid compositionof triacylglyceride stores is highly influencedby the fatty acid composition of insect diets.Despite feeding on the same diet, however, thetriacylglyceride stores of diapausing individualsfrom several species contain more unsaturatedfatty acids, whereas the triacylglyceride storesof nondiapausing individuals contain more sat-urated fatty acids (17, 40, 63). Triacylglyceridestores can only be enzymatically mobilized fromintracellular lipid droplets when they are in liq-uid form and when the lipid droplet surfaceproteins can appropriately interact with lipoly-tic enzymes; therefore, greater unsaturation indiapause-destined individuals may be impor-tant for fat mobilization at low temperatures.This idea receives support from both the liter-ature on mammalian hibernators, showing thatground squirrels and chipmunks fed diets highin saturated fats are more likely to avoid hi-bernation and have shorter hibernation peri-ods with higher body temperatures (27, 89),and the literature on invertebrate cold toler-ance, showing a substantial increase in fattyacid unsaturation associated with cold acclima-tion and adaptation to cold climates (52, 65,79). In addition to triacylglycerides, alterationsin lipid metabolism associated with modifica-tions of cell membrane fluidity and depositionof cuticular waxes and hydrocarbons have beennoted during the diapause preparatory period(76, 110, 117).

Like most animals, the primary carbohy-drate reserve in insects is the polysaccharideglycogen. Insect muscles, particularly flightmuscles, can store substantial quantities ofglycogen that are catabolized during exercise,but the fat body is the primary site of glyco-gen synthesis and storage, and fat body glyco-gen stores can be rapidly converted to glucose

or the disaccharide trehalose for transport toother tissues (5). Diapause is associated withqualitative and quantitative shifts in glycogenmetabolism. Prior to diapause many insects ac-cumulate large glycogen reserves, and as withfat stores, diapausing individuals often accumu-late greater glycogen reserves than their non-diapausing counterparts, although this is notalways the case (26, 107, 120).

Fat body glycogen reserves play two majorroles in diapausing insects: They are convertedto glucose or trehalose for transport out of thefat body to tissues for fueling catabolism, andthey are metabolized to produce a variety ofsugar-alcohol and sugar-based cryoprotectantmolecules. Glycerol and sorbitol are the mostcommon cryoprotectant molecules found in in-sects, but some species synthesize other poly-ols such as ethylene glycol, erythritol, manni-tol, ribitol, and threitol, as well as sugars with acryoprotective role including trehalose and glu-cose (33). The production of cryoprotectantsfrom glycogen can occur either as part of thediapause preparatory program without prior ex-posure to low temperatures or in response tocold exposure in diapausing or nondiapausingindividuals. For example, when held at constanttemperatures, diapausing pupae of the flesh fly,Sarcophaga crassipalpis, contain greater quanti-ties of glycerol and are more cold tolerant thannondiapausing individuals, illustrating that in-creased glycerol levels are part of the diapauseprogram (33).

Increased amino acid concentrations arepresent in the blood of some diapausing in-sects, but it is unclear whether these additionalamino acids primarily play a role in nutrientstorage or cold and desiccation resistance (71,77). Many diapausing insects store amino acidsin the form of specialized storage proteins, ini-tially termed diapause proteins, but most be-long to the storage hexamerin family of in-sect proteins, which are also accumulated inlesser quantities in nondiapausing insects (16,36). Storage proteins are typically accumulatedprior to diapause, and during diapause theirconstituent amino acids may be used for bothanabolic activities in maintaining turnover of


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active protein pools, such as molecular chaper-ones, and catabolic respiratory metabolism, aswell as supporting anabolic and catabolic rolesin postdiapause functions such as resumptionof development (36). Several studies indicatethat storage proteins may continue to be syn-thesized at low levels during diapause (42, 100).Whether storage proteins produced during di-apause are playing roles in amino acid storageand intermediary metabolism or some otherfunction, such as humoral defense or cold tol-erance, is not known, but their rapid disappear-ance following diapause termination suggests arole in postdiapause tissue remodeling.

METABOLIC DEPRESSION ANDNUTRIENT MOBILIZATION

In addition to accumulating reserves duringthe preparatory period, diapausing individu-als save on metabolic costs by suppressingintermediary and respiratory metabolism. Al-though metabolic depression is a near univer-sal aspect of diapause, the degree of depressioncan vary widely among species and diapausestrategies from a mild 15% suppression in theflight-capable diapausing adults of the monarchbutterfly (19) to the extreme 90% suppressionobserved in diapausing flesh fly pupae (35, 85).Metabolic depression in diapause results froma combination of ecological and physiologi-cal factors (48). Metabolism is proportional totemperature in diapausing insects, as in all ec-totherms, and careful site selection can reducemetabolic stress (56, 57, 97, 113). The low tem-peratures of winter greatly favor metabolic de-pression, but summer and tropical diapauses arealso common and metabolic depression is par-ticularly important in these species (31).

Most diapausing insects are not activelygrowing or reproducing, and cell cycle ar-rest, decreased synthesis of proteins and othermolecules, and genomic remodeling associatedwith reduced transcription all contribute to de-creased requirements for energy or anabolicsubstrates (36). Whole-organism maintenancecosts can be reduced by allowing unneces-sary tissues, such as gut or flight muscle, to

atrophy (29). However, diapausing animalsmust actively maintain some tissues, such asthe brain and imaginal discs, that are criticalto surviving diapause and performing post-diapause functions. Therefore, metabolic de-pression is not just a reduction of all cellularprocesses, but is a selective reduction of someprocesses, such as growth and reproduction,and an increase in others, such as stress resis-tance mechanisms, yielding a net decrease inoverall metabolic demand (36). An importantquestion is, Which modules of intermediarymetabolism are decreased during diapause, andwhich are maintained or enhanced?

In addition to resource conservation,metabolism may be rearranged during diapauseto promote stress resistance. Hypoxia/anoxiastress is a common risk for diapausing in-sects, especially those in soil that may be-come inundated with rain, snow, or ice. Somediapausing insects show substantial resistanceto hypoxia/anoxia stress, such as diapausingflesh fly pupae that survive six days of anoxia,whereas nondiapausing pupae perish after oneday (66). In addition to resource conservation,metabolic depression may enhance resistanceto hypoxia/anoxia stress. Indeed, metabolicsuppression has been associated with hypoxicoverwintering states in numerous ectothermsincluding the roundworm, Caenorhabditis el-egans, turtles, fish, and snails (39, 74, 103).In these examples, animals decrease aero-bic metabolism and shift largely to anaerobicmetabolism, favoring the activity of glycoly-sis and gluconeogenesis, the pentose phosphateshunt, and the phosphoenolpyruvate carboxy-kinase (PEPCK)-succinate pathway to gener-ate ATP and reduce equivalents. Are diapaus-ing insects following this same shift away fromaerobic metabolism during diapause? A series ofrecent transcriptomic and metabolomics stud-ies of adult reproductive diapause in Drosophilamelanogaster (7), larval diapause in the pitcherplant mosquito, Wyeomyia smithii (37), and pu-pal diapause of the flesh fly S. crassipalpis (84)show diapause enrichment in key transcriptsfor glycolysis and gluconeogenesis. Diapausingflesh fly pupae have increased glucose, glycerol,


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Respiratory quotient(RQ): the ratio of ananimal’s oxygenconsumption tocarbon dioxide release,reflecting specificforms of energyutilization

and pyruvate (75, 76), a difference in metabo-lites consistent with a shift away from aerobicmetabolism and towards anaerobic metabolism.In the above mentioned studies, individualswere never exposed to hypoxia or anoxia, sug-gesting that a preponderance for anaerobicmetabolism at the time of metabolic suppres-sion is a preprogrammed component of dia-pause development.

Further work is needed to determinewhether diapausing insects generally attainmetabolic depression by specifically suppress-ing aerobic metabolism while maintaininganaerobic pathways, how it relates to theirdiapause life histories, and what biochemicalmechanisms regulate the shift toward anaerobicmetabolism in diapause. One promising mech-anism for coordinating the shift from aerobicto anaerobic metabolism in diapausing insectsis the transcriptional suppressor hairy, revealedby a recent study of hypoxia-selected lines inD. melanogaster (119). hairy transcription wasupregulated in hypoxia-selected lines, and im-portant aerobic respiration genes in the citricacid cycle that had lower expression in hypoxia-selected lines also contained hairy bindingelements in their regulatory regions. hairy loss-of-function mutants were more susceptible tohypoxia stress and did not show coordinateddownregulation of TCA cycle transcripts inresponse to hypoxia, further reinforcing therole of hairy as an important metabolic switch.Could hairy also act as a metabolic switchin diapausing insects? Diapausing pupae ofthe flesh fly, S. crassipalpis, suppress aerobicmetabolism in favor of anaerobic metabolismduring diapause-induced metabolic depression,and hairy transcript abundance is substantiallygreater in diapausing pupae than in nondia-pausing pupae (84). However, hairy expressionlevels apparently do not differ between di-apausing and reproductive D. melanogasteradults (7), necessitating more work to establishthe generality and importance of hairy as ametabolic switch in diapausing insects.

Although metabolic depression conservesnutrient reserves, reserves are substantially de-pleted during diapause. Many studies show

depletion of one reserve material or another,but few carefully track the utilization of multi-ple reserve classes throughout diapause. Stud-ies that do track multiple nutrient classes in-dicate reserve mobilization is dynamic and notuniform throughout diapause. For example, inthe adult diapause of the mosquito Cx. pipiens,females deplete glycogen stores during the firstmonth of diapause and then switch to use lipidsas shown by both radiotracer tracking (120) andexpression studies of β-oxidation genes (96).Flesh flies show the opposite pattern wherelipids are depleted early in diapause followedby a shift to other substrates (1). Further, a res-piratory quotient (RQ) study in diapausing leaf-cutter bee larvae suggests lipid catabolism (RQnear 0.7) early in diapause, followed by a shift tocatabolism of amino acids, glycogen, or a mix-ture later in diapause (RQ values from 0.8 to1.0) (116). Specific nutrient subclasses may alsobe selectively utilized during diapause. For ex-ample, within the larger fatty acid pool storedas triacylglycerides, unsaturated fatty acids de-crease more rapidly than saturated fatty acidsduring diapause (17, 40, 63). Although selec-tive mobilization of unsaturated fats has beensuggested as an adaptation to low temperatures,mammals and birds also show preferential mo-bilization of unsaturated fatty acids across arange of conditions, suggesting that preferen-tial depletion of unsaturated fatty acids may be ageneral pattern of mobilization, not a diapause-specific pattern (82, 83).

In addition to longer-term shifts in nutrientutilization, rapid changes also occur. Forexample, diapausing larvae of the goldenrodgall fly, Eurosta solidaginis, convert glycogenstores to glycerol in response to low temper-ature in the fall (104). However, conversionof glycogen to glycerol is reversible andtemperature dependent, so that as insectswarm in the spring, much of the glycerolis recovered and stored again as glycogen.Glycerol production remains environmentallysensitive during diapause wherein short-termlow-temperature spells are accompanied byincreased glycerol production and rewarmingdrives reconversion to glycogen. The dynamic


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Oxygen (O2)consumption bouts:a cyclic infradianpattern of metabolismthat persiststhroughout diapausein certain Diptera andLepidoptera pupae

conversion and reconversion between glycogenand glycerol are regulated by a simple, elegantmechanism modifying the activity of glycogenphosphorylase, a key glycogen-mobilizingenzyme. Temperature-dependent activationof glycogen phosphorylase occurs under coldconditions because low-temperature exposurein the 0◦C–5◦C range inactivates glycogenphosphorylase phosphatase, while the reduc-tion in glycogen phosphorylase kinase activityat 0◦C–5◦C is less pronounced and in line withQ10 predictions for the enzyme (20). There-fore, glycogen phosphorylase is more likelyto be activated and provide glucose substratesfor glycerol synthesis at low temperatures,providing direct environmental control ofmetabolic flux via protein phosphorylation re-actions. Whereas short-term alterations in theintermediary metabolism of other substratesand products are not well known, it is clear thatother mechanisms, such as some heat shockproteins and desaturases that modify mem-brane lipids (21, 33, 36), can respond rapidly toenvironmental stress during diapause and mustpresumably mobilize materials from reserves tosynthesize new proteins and membrane lipids.

Cyclic Bouts of Metabolismduring Diapause

The metabolic rate during diapause is not con-stant in all insects but instead may be char-acterized by periodic bouts of high metabolicactivity, lasting 1–2 days at 25◦C, interspersedbetween 4 and 5 days of low metabolic activ-ity that is barely detectable. These cycles werefirst noted in diapausing pupae of sarcophagidflies (35) but have also been reported in dia-pausing pupae of several lepidopteran species(24, 25). Not all species exhibit such cycles, andit remains unclear why some species are cyclicand others are not. These cycles should not beconfused with the better known cyclic dischargepatterns of CO2 of saturniid and other large lep-idopteran pupae (51, 93). During the saturniidCO2 bursts, O2 consumption remains constant,but the cycles observed in Sarcophaga are indeedcycles of O2 consumption that thus represent

distinct pulses of metabolic activity that persistthroughout diapause.

Metabolic cycles in flesh fly pupae are closetogether in early diapause, become further apartin mid-diapause, and then become closer to-gether again near the end of diapause (35). Theonset of the metabolic pulse is abrupt (98),suggesting a rapid switching mechanism thatrapidly turns on the metabolic machinery. Sev-eral lines of experimental evidence suggest thatthese metabolic cycles are driven by JH (32, 34).

The interesting question is why diapaus-ing flesh fly pupae display cyclic bouts ofmetabolic activity rather than maintain a con-stant low metabolic rate. Protein synthesispeaks during O2 consumption pulses (59), andselect genes, such as the transcript encod-ing apurinic/apyrimidinic (AP) endonuclease,a protein that repairs DNA damage in oxi-dation and hypoxia injury, show peak expres-sion during the trough of the cycle (23). Pre-sumably it is metabolically more efficient forflesh flies to dramatically suppress metabolismmost of the time and to just briefly stoke upthe metabolic furnace when needed. Possiblythe fly uses these bouts of metabolic activity togenerate ATP, replenish other key metabolites,boost its stress defense, and repair damage whileburning off metabolic end products that may ac-cumulate during the trough of the cycle. Suchcycles underscore the dynamic nature of en-ergy utilization that can operate in some speciesduring diapause. These cycles of metabolismhave a striking resemblance to the regular peri-ods of arousal noted in mammalian hibernators(18, 111), suggesting a common advantage forcyclic metabolic activity during diverse types ofdormancy.

ENERGY SENSING

We argue that some sort of energy-sensingmechanism operates in diapausing insects, en-abling them to assess levels of reserves in theirbody. Such information could be used dur-ing the diapause preparatory period to affectthe decision to enter diapause (have enoughreserves been stored?) or during diapause to


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Energy sensing:refers to the ability ofan animal to accuratelyassess its energeticstate based on reservesand current feedingstate

Insulin signaling:a signal transductionpathway affectinggrowth, reproduction,and carbohydrate andlipid metabolism thatis activated by thepresence of insulin oran ILP

ILP: insulin-likepeptide

Dauer larvae:a dormant state innematodes equivalentto diapause in insects

affect the decision to terminate diapause (arereserves running low?). Indeed, small larvae ofthe blow fly Calliphora vicina avert diapause orterminate diapause earlier than well-fed larvae(90), suggesting that such an energy sensor isoperating. Experimental manipulations of therate of metabolic activity in diapausing flesh flypupae also suggest this possibility (32). Hightemperature or application of a JH analog ele-vates the diapause metabolic rate, resulting ina shorter diapause. A comparison of metabolicrates and diapause durations under these di-verse conditions suggests that diapause couldbe terminated when reserves reach some criti-cal set point. When the metabolic rate is highthe available energy is consumed quickly, andwhen the metabolic rate is low this set pointis reached much later, yielding a longer dia-pause. Presumably, most insects enter diapausewith more than adequate reserves, and a limit onsuch reserves is not what normally determinesthe duration of diapause, yet a modest adjust-ment in either the amount of stores or rate ofutilization could shorten or lengthen the dura-tion of diapause in some species.

Although it was once thought that fat bodycells were just depots for accumulating stores,our understanding of adipocytes has blossomedin the past two decades so that in both mammalsand invertebrates adipocytes are recognized toactively participate in regulating metabolismboth through localized subcellular mechanismsand in endocrine interactions with the gut andbrain. This recognition has led to a flurry ofstudies on D. melanogaster and a few on otherinsects such as mosquitoes and the hawk moth,Manduca sexta, reinforcing the idea that fatbody cells play critical roles in nutrient sensing,nutritional homeostasis, feeding behaviors,and coordinating growth and reproductionwith nutrition (5, 8, 10). Similarly, a recenthigh-throughput study of 350 transgenicD. melanogaster lines that either suppress or hy-peractivate specific neuronal groups in the brainrevealed two sets of neurons that when silencedproduced very fat flies and when overactivatedproduced very lean flies (2). This findingcrystallizes the view that the insect brain has

distinct groups of neurons that regulate feedingand nutrient homeostasis similar to the verte-brate brain-hypothalamic axis. Unfortunately,few experiments have directly explored energysensing, feeding and digestive physiology, andnutrient mobilization in diapausing insects,and the mechanisms we propose are simplypossibilities that have not yet been criticallyexamined experimentally. Below we discussinsulin signaling, which has been implicated asan important pathway in nutrient regulation,growth, and dormancy in insects and nema-tode worms, and we suggest some additionalcandidate mechanisms for nutrient sensingand metabolic reorganization in diapausinginsects.

Insulin Signaling

The insulin signaling pathway, best knownfor its role in regulating carbohydrate and fatmetabolism in mammals, is highly conservedand a promising candidate for regulating re-serves in insect diapause. As in mammals, in-sulin signaling has roles in metabolism andgrowth in nematodes (39) and insects (8, 10,15, 114). Although mammals have relatively fewinsulin-like peptides (ILPs), many members ofthis family are present in insects (114): EightILPs are known from the mosquito Ae. aegypti,but more than 30 are present in the silkmothB. mori. In spite of this wealth of ILPs, all ormost of the ILPs appear to exert their effectthrough a single receptor (114). What it meansfor insects to have such an array of ILPs is notclear but is matched by diverse physiologicalfunctions linked to ILPs, including growth anddevelopment, metabolism, reproduction, andcaste determination in social insects (114).

The centrality of insulin signaling to energystorage and utilization in mammals suggeststhat this pathway could be central to energyissues during insect diapause. A link to diapausewas first suggested by elegant work definingmolecular events in dauer larva formation (adormant state equivalent to diapause) in thenematode C. elegans. Like insects in diapause,C. elegans dauer larvae accumulate fat reserves


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FOXO: Forkheadtranscription factor

and enter an arrested state that has most of theattributes of insect diapause (39). Several keygenes linked to dauer formation in C. elegans,referred to as dauer formation (daf ) genes,proved to be orthologs of genes in the insulinsignaling pathway. In D. melanogaster, disrupt-ing insulin signaling shuts down reproductionand increases energy stores, inducing a phys-iologic state reminiscent of the natural adultdiapause in this species (106). JH terminatesreproductive diapause in D. melanogaster, andthe inhibition of reproduction and accumu-lation of reserves can be reversed by applyingexogenous JH mimics (105).

Insulin signaling is apparently also involvedin both shutting down reproduction andregulating fat accumulation associated withadult diapause in the mosquito Cx. pipiens (94).Knocking down the insulin receptor (InR)in nondiapausing females with dsInR blocksovarian development, simulating the diapausestate. This blockage can be reversed with JH, ahormone essential for the initiation of follicledevelopment, and the response is similar to theJH mitigation of impaired insulin signaling onaging in D. melanogaster (105). Many of the ef-fects of insulin signaling on diapause-like statesin C. elegans and D. melanogaster are mediatedby the fork-head transcription factor (FOXO),a critical downstream member of the path-way. FOXO is suppressed in the presence ofinsulin, but in the absence of insulin FOXO isactivated and translocated from the cytoplasminto the nucleus where it initiates a numberof responses including fat accumulation inD. melanogaster (8). During the prediapauseperiod, adult females of Cx. pipiens eschewblood feeding and increase sugar feeding,changing their feeding behavior and digestivephysiology to accumulate much greater fatreserves compared with nondiapausing females(88). If FOXO expression is knocked downusing RNAi in diapause-destined females ofCx. pipiens, the females fail to accumulate thehuge fat reserves characteristic of diapause (94),thus suggesting a critical role for the insulinsignaling pathway in fat reserve accumulation.Not all ILPs appear to contribute to diapause

regulation in Cx. pipiens; ILP 1, but not ILP 2or ILP 5, regulates the response (95).

Across insects, diapause states are oftenmaintained by modulating the titers of the ma-jor developmental hormones JH and ecdys-teroids, and insulin may be a critical signalingsystem upstream of both JH and ecdysteroids.Insulin signaling has been implicated in main-taining and eventually terminating the adult re-productive diapause of D. melanogaster and Cx.pipiens mosquitoes by modulating JH titers, andadding exogenous JH to diapausing adults ter-minates diapause and rescues the nondiapausereproductive phenotype. Similarly, many pupaldiapauses and some larval diapauses are char-acterized by decreased ecdysteroid productionand terminated by application of exogenousecdysteroids (36). Insulin signaling stimulatesecdysteroid production by ovaries in mosquitoreproduction (15); could it play an importantrole in terminating larval and pupal diapauseby stimulating ecdysteroid production? Pupaldiapause of the butterfly Pieris brassicae is char-acterized by the absence of ecdysteroid produc-tion, and application of exogenous ecdysteroidscan terminate diapause and initiate adult mor-phogenesis (4). Injecting bovine insulin intodiapausing pupae of P. brassicae stimulatesecdysteroid production and terminates dia-pause (4). Enhanced insulin signaling is alsoinvolved in terminating the larval dauer statein C. elegans, wherein insulin signaling stimu-lates production of dafachronic acids, a blendof steroid hormones that act via the DAF-12 nuclear hormone receptor to resume lar-val development (39). Therefore, we expectthat insulin signaling plays an important rolein both metabolic suppression during diapauseand the resumption of development at diapausetermination.

TOR Signaling

Target of rapamycin (TOR) signaling is a sis-ter pathway that interacts with insulin signal-ing to regulate body size and nutritional sta-tus in insects and vertebrates (44, 68, 101). Thefat body acts as a nutrient-sensing organ in the


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TOR: target ofrapamycin

AKH: adipokinetichormone

PKA: cyclic AMP-dependent proteinkinase A

LSD-1: lipid storagedroplet surfaceprotein-1

context of TOR signaling in D. melanogaster,wherein amino acid uptake by the fat bodyduring larval feeding enhances TOR activityand stimulates larval growth (22, 41). Simi-larly, the fat body acts as an important nutrient-sensing organ controlling the initiation ofvitellogenesis in adult mosquitoes by regulat-ing the flow of amino acids derived from ei-ther a recent blood meal or protein stores inthe fat body into newly synthesized yolk pro-teins (6, 49). It is unknown how the fat bodyinterprets and transduces amino acid availabil-ity into enhanced TOR signaling to coordinategrowth and reproduction, but several fat bodyamino acid transporters have been implicated inactivating TOR signaling (22, 41). The role ofTOR in coordinating both growth and repro-duction in a nutrition-dependent manner sug-gests it could play important roles in three con-texts: differential nutrient accumulation duringthe diapause preparatory period, nutrient uti-lization during diapause, and the shift from de-velopmental arrest during diapause to activegrowth or reproduction at diapause termina-tion. Similarly, other mechanisms of nutrienthomeostasis may also exert their effects, at leastpartially, by modulating insulin signaling.

Adipokinetic Hormones

The insect adipokinetic hormones, AKHs,are a family of small peptides that regulatemobilization of lipids, glycogen, and evenamino acids (72, 112). Originally characterizedfor their role in mobilizing flight fuels, AKHfunction in D. melanogaster and the silkwormB. mori is important for nutrient homeostasis,including accumulation and mobilization oflipid and glycogen reserves (58, 70). Althoughevidence for the involvement of AKH in dia-pause is currently limited, one study of AKHin the firebug Pyrrhocoris apterus shows thatfemales in adult reproductive diapause mobilizeapproximately twice as much lipid into theblood as nondiapausing reproductive femaleswhen injected with synthetic migratory locustLocusta migratoria AKH-I peptide or extracts ofthe P. apterus corpora cardiacum, the gland that

secretes endogenous AKH (99). This findingsuggests that diapausing adults have greatersensitivity to the lipid-mobilizing effects ofAKH, but differences in AKH sensitivity as ageneral pattern in diapause are unknown.

Differences in AKH sensitivity for nutrientmobilization have been shown across life stagesin several insects (72, 112). For example, thesame AKH peptide prompts glycogen mobi-lization in larvae but mobilizes lipid in adultsof the hawk moth, M. sexta (5). The migratorylocust L. migratoria produces multiple distinctAKH peptides that differ in substrate mobiliza-tion, perhaps revealing specialized functions foreach different peptide in nutritional homeosta-sis. Although all locust AKH peptides mobilizetriacylglycerides, AKH-I shows greater abilityto mobilize lipids than AKH-II or AKH-III,while AKH-II shows a greater affinity for mobi-lizing glycogen (112). In addition to differencesin the dose-dependent propensity to mobilizelipids, AKH-I mobilizes diacylglycerides witha fatty acid profile distinct from AKH-II andAKH-III, further suggesting specialized rolesfor each AKH peptide in mobilizing differentfuel classes (109).

What factors promote specific mobilizationof discrete nutrient classes or subclasses byAKH between different life stages or amongdifferent AKH peptides? In M. sexta, AKH acti-vates cAMP-dependent protein kinase A (PKA)in adult fat body cells, which then phospho-rylates triacylglyceride lipase and lipid storagedroplet surface protein-1 (LSD-1), a proteinthat localizes to the surface of lipid dropletsin fat body cells, similar to the vertebrate per-ilipins (5, 67). In M. sexta, phosphorylation ofLSD-1 at the surface of the lipid droplet appearsnecessary for triacylglyceride lipase to mobi-lize stored triacylglycerides from lipid droplets.LSD-1 is present only in adult fat body cells,which mobilize lipids in response to AKH, andis absent from larval fat body cells, which mo-bilize glycogen rather than lipids in response toAKH, prompting the suggestion that LSD-1controls stage-specific differences in energymobilization in M. sexta (5). Investigation oflipid droplet surfaces in D. melanogaster shows


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AMPK: AMP-activated proteinkinase

Neuropeptide F(NPF): theinvertebrate orthologof vertebrateneuropeptide Y

Foraging (For):a locus coding for aconserved cGMP-dependent proteinkinase

a complex mixture of dozens of proteins, someof which are implicated in metabolism and lipidmobilization, concordant with studies of mam-malian lipid droplets (5, 9, 10, 67). Changes incomposition of lipid droplet surface proteinscould contribute to the differences in fuel mobi-lization observed between diapausing and non-diapausing insects, as well as shorter-term dif-ferences in fuel mobilization during diapause,either through their ability to modulate AKHaction or through other undescribed routes.

Other Mechanisms of Energy Sensingand Nutrient Mobilization

AMP-activated protein kinase (AMPK) is an-other promising candidate. AMPK is often re-garded as part of the cellular energy-sensingsystem because this enzyme becomes activatedby phosphorylation in response to high ratiosof AMP:ATP, and then AMPK itself furtherphosphorylates a series of downstream proteinsthat control flux through metabolic pathwaysaffecting appetite, ATP production, and thesynthesis/degradation of lipid and carbohy-drate reserves (50). In mammals, suppression ofAMPK activity leads to increased lipid biosyn-thesis and storage, whereas activation leads tolipid and carbohydrate catabolism. Further-more, recent work on AMPK suggests that itmay bind directly with glycogen, essentially act-ing as a cellular fuel gauge for glycogen (73),and that it interacts with insulin/TOR signal-ing to regulate synthetic activity underlyinggrowth, thereby directly linking growth withenergy supplies (46). Although AMPK func-tion has been best studied in mammals, AMPKhas similar functions in D. melanogaster (80).AMPK activity is implicated in developmentalsuppression and metabolic rate depression inhypoxic Trachemys scripta turtles (87) and esti-vating Otala lactea land snails (86), but it doesnot appear to be important in hibernating Sper-mophilus tridecemlineatus squirrels (53). A recentmicroarray study of diapausing S. crassipalpisflesh fly pupae showed that transcripts match-ing the AMPK α, β, and γ subunits were up-regulated in diapausing pupae compared with

nondiapausing pupae (84). AMPK is activatedposttranslationally by phosphorylation, so fur-ther work on protein abundance and activity indiapausing flesh fly pupae is clearly needed, butthis regulatory enzyme is a likely candidate forregulating reserves in diapause.

In addition, several other signaling path-ways stand out as promising candidates formediating feeding and nutritional homeosta-sis in diapause-destined and diapausing in-sects. The invertebrate neuropeptide F (NPF),homologous to the vertebrate hypothalamicneuropeptide Y, is produced in medial neurose-cretory cells of the D. melanogaster brain andplays roles in both feeding behavior and insulinsignaling (14, 115). Overexpression of NPFcauses prolonged feeding in D. melanogasterlarvae and NPF loss-of-function mutantsfeed less. Similarly, higher expression of thecGMP-dependent protein kinase, For, has beenassociated with enhanced feeding and foragingbehavior in D. melanogaster, C. elegans, honeybees, and ants (62). In D. melanogaster, individ-uals carrying a naturally occurring For allele as-sociated with higher PKG expression and en-hanced feeding also accumulate greater lipidreserves and have apparently greater glucosemobilization during starvation (60, 61). Coulddiapause-destined individuals become hyper-phagic and accumulate greater nutrient reservesby upregulating NPY, For, or other feeding-behavior genes that alter the brain–gut–fat bodyaxis?

The greater nutrient reserves accumulatedin diapause-destined insects may be facilitatedby hypertrophy of fat body cells, with each cellstoring more, greater proliferation of fat bodycells so there are more cells available for stor-age, or both. Several candidates for regulatingfat body hypertrophy and proliferation havebeen identified in D. melanogaster. For example,flies with partial-loss-of-function mutations inthe transcriptional repressor gene adipose showsubstantial triacylglyceride accumulation by fatcell hypertrophy, but overexpression of adiposein wild-type flies leads to decreased triacylglyc-eride accumulation in fat body cells (47). To ourknowledge, direct comparisons of the number


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of fat body cells in diapausing and nondia-pausing insects have not been made, but manyinsects that diapause as fully developed larvae orpupae initiate the prediapause developmentaltrajectory as embryos; thus, there is ample timefor enhanced fat cell proliferation during thediapause-preparatory program (30). Illustratingthe importance of fat cell number for storage, arecent RNAi screen for obesity phenotypes inD. melanogaster identified several dozen genesassociated with enhanced triacylglyceride orglycogen storage (81). Among these fat bodyobesity genes were hedgehog-signaling pathwaymembers that enhanced fat body cell prolifera-tion, leading to phenotypes with greater triacyl-glyceride stores. Could the hedgehog-signalingpathway and perhaps even some of these samegenes be involved in the greater accumulationof nutrient reserves in diapause-destinedinsects? Comparative studies of fat body cellhypertrophy and number are needed to untan-gle the relative roles of these two processes indiapause-induced reserve accumulation.

CHALLENGES OFCLIMATE CHANGE

Global warming has already had an impacton insect populations, as demonstrated in theNorthern hemisphere by northward invasionsof more southerly species and shifts in photore-sponsiveness and voltinism to accommodatelonger growing seasons (12, 13, 54). There isenough naturally segregating genetic variationin photoperiodic responses in some insects toprovide the grist for rapid evolutionary shifts incritical photoperiod for diapause. In the pitcherplant mosquito, Wyeomyia smithii, a shift towarda shorter, more southern critical daylength cor-responding to a longer growing season was de-tectable within a 30-year period (11), and thecritical photoperiod in a Japanese population ofthe fall webworm, Hyphantria cunea, was short-ened by 13–19 min over a 7-year period, result-ing in a concomitant shift from bivoltinism totrivoltinism (43).

Implicit in this warming trend is an issuecritical to energy utilization during diapause, a

feature of global warming that is perhaps un-derappreciated. As discussed above, insects relyon low temperatures of winter to help suppressmetabolism and conserve energy stores. Awarmer winter could thus mean that an insectwith a tight energy budget may indeed depleteits reserves too early and thus jeopardize sur-vival and/or postdiapause fitness. For example,overwintering populations of the monarchbutterfly, Danaus plexippus, appear to be on atight energy budget, with fat content droppingover a two-month period from 71% lean dryweight in late November to 36% in late January(19). The monarch female must still retainenough fat at the end of diapause to migrate toa suitable larval habitat for oviposition. Coolnights are critical for suppressing the metabolicrate at these monarch overwintering sites, andjust a slight temperature elevation would ap-pear to jeopardize the overwintering success ofthe butterfly, especially at some of the currentoverwintering sites in southern California. Justhow critical a slight temperature elevation maybe is demonstrated in observations comparingsurvival and reproductive success in individualsof the goldenrod gall fly, Eurosta solidaginis,that overwinter above the snow in standinggoldenrod stems or below the snow in brokenstems (57). Although the mean temperaturein the better-insulated galls held below thesnow was only 0.6◦C higher than in galls foundabove the snow, fewer adults emerged fromthe warmer galls and their reproductive outputdropped 18%, a difference possibly attributableto the more rapid depletion of reserves in thewarmer individuals. Thus, what appears to bea small temperature change can be expectedto have a considerable impact on the deple-tion of energy reserves and consequently onpostdiapause energetics and fecundity.

Alternatively, we can anticipate energy-related benefits of a warming planet for cer-tain species. As discussed earlier, the blow fly,C. vicina, does not appear to adjust its fat stor-age or utilization rate as a function of diapauseor latitude (91), and warmer winters are trans-lated into a shorter larval diapause in this mul-tivoltine, facultative-diapausing species. This,


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in turn, enables the fly to carry over more of itslarval reserves into adulthood, possibly enhanc-ing fecundity. Impacts on diapause energetics,both positive and negative, as well as pheno-typic plasticity and generic variation in the in-sect’s ability to respond to climate change, arelikely to have far-reaching implications for in-sect populations in our changing world.

FINAL PERSPECTIVES

By understanding how insects manage their en-ergy budgets during diapause we can identifyone of the critical dimensions defining the lim-its of insect survival in seasonal environments.We anticipate that such information could helpexplain current species distributions and willbe essential for predicting success of invasivespecies, the movement of native species intonew habitats, and new species interactions suchas insects shifting onto new host plants, predic-tions that are especially important as we lookahead to global warming trends that will likelycompromise current insect energy budgets. Be-cause many insects appear to be on a tight en-ergy budget, the potential of capitalizing on thisvulnerability by searching for new agents thatcould selectively prevent fat accumulation, el-evate diapause metabolism, or deplete energyreserves prematurely would appear to be a tac-tic that could be exploited to manipulate pestpopulations.

Although management of an energy bud-get is critical for understanding the narrowquestion of how insects survive adverse con-ditions and synchronize development, diapausealso offers a good model for probing more basic

questions related to energy storage and utiliza-tion. For example, we show that many insectsmake a clear decision to store fat at a particu-lar time during their prediapause development.How is such a decision made? With the chal-lenges of obesity and diabetes plaguing the de-veloped world, knowing how such physiologicdecisions are made is a question of huge signif-icance to human health. Are there lessons thatcould be learned from diapause? Similarly, dur-ing diapause, insects switch between the utiliza-tion of lipid and nonlipid sources. How are suchprocesses regulated? The ability to turn downthe metabolic furnace is a trait that is especiallyimpressive during insect diapause. Understand-ing how this is done may offer useful tips for de-veloping strategies of tissue storage that amelio-rate hypoxia-reperfusion injury, a high prioritygoal for maintaining healthy tissues for humanorgan transplants. Although studies of nutri-ent homeostasis in D. melanogaster and othermodel organisms, facilitated by large commu-nity resources for novel screening technologies,have revolutionized our understanding of con-served mechanisms of energy homeostasis, westrongly advocate a place in this field for nontra-ditional models. Although nontraditional mod-els, such as the flesh fly, S. crassipalpis, may nothave the genetic resources of D. melanogaster,diapausing flesh fly pupae display much moredrastic metabolic depression during diapause.By choosing to study nutrient homeostasis inorganisms from the extremes of the diapausespectrum, we may find new mechanisms thatare highly conserved but overlooked in modelorganisms that show less pronounced diapauseresponses.

SUMMARY POINTS

1. Many, but not all, insects store additional energy reserves during the preparatory phaseof diapause. Triacylglycerides are the dominant form of energy storage, but glycogenreserves and hexameric storage proteins are also frequently accumulated.

2. Metabolic depression, facilitated by low winter temperatures, is an essential mechanismfor conserving energy stores. Metabolic depression is especially important in summerand tropical diapauses that must also contend with high temperatures.


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3. Utilization of reserves during diapause is a dynamic process. Switching from one typeof reserve to another as diapause progresses appears to be common. Infradian cycles ofmetabolism, akin to the arousal periods of mammalian hibernators, are evident in somediapausing Diptera and Lepidoptera.

4. Insects are capable of evaluating the abundance of their energy stores and in some casesuse this information to avert diapause or terminate diapause prematurely if stores arelow, but the mechanism of energy-sensing remains unknown.

5. Insulin signaling appears to be an important pathway regulating storage of diapauseenergy reserves, but the mammalian hibernation literature and other studies suggestadditional pathways that are likely involved in diapause energy management.

6. Modest temperature elevation can dramatically affect energy budgets that are alreadytight during diapause. Thus, rising global temperatures are likely to significantly affectseasonal and geographic distributions of insects.

FUTURE ISSUES

1. At the organismal level, we know surprisingly little about how the management of di-apause energy reserves dictates patterns of seasonal distribution. This issue becomesespecially important as the temperature of our planet increases and thus places new con-straints on energy budgets. Although there is some plasticity and underlying genericvariation in this response, it is unclear what the limits of tolerance may be.

2. At the suborganismal level, much work remains in defining the fine details of themetabolic switches and pathways that lead to metabolic depression and the dynamicchanges in energy utilization that characterize diapause.

3. At the molecular level, the regulatory pathways used by insects for accumulating re-serves and for regulating the utilization of those reserves as diapause progresses remainlargely unknown. How does an insect make the decision to switch from one type of re-serve to another midway through diapause? How does it know when its energy reservesare becoming critically low and how does it use this information to trigger the end ofdormancy?

DISCLOSURE STATEMENT

The authors are not aware of any affiliations, memberships, funding, or financial holdings thatmight be perceived as affecting the objectivity of this review.

ACKNOWLEDGMENTS

We acknowledge that the work of many of our colleagues could not be included because of spacerestrictions. While preparing this review we were supported by funds from NSF IOS-641505,USDA-TSTARC-09051246, and the Florida State Agricultural Experiment Station to D.A.H.and by NSF IOS-0840772, USDA NRI 2006-35607-16582, and NIH RO1-AI1058279 to D.L.D.


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NOTE ADDED IN PROOF

We would also like to point out a very useful recent review of diapause molecular biology publishedwhile this article was in press.

MacRae TH. 2010. Gene expression, metabolic regulation and stress tolerance during diapause.Cell Mol. Life Sci. 67:2405–24


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EN56-Frontmatter ARI 28 October 2010 7:29

Annual Review ofEntomology

Volume 56, 2011Contents

Bemisia tabaci: A Statement of Species StatusPaul J. De Barro, Shu-Sheng Liu, Laura M. Boykin, and Adam B. Dinsdale � � � � � � � � � � � � � 1

Insect Seminal Fluid Proteins: Identification and FunctionFrank W. Avila, Laura K. Sirot, Brooke A. LaFlamme, C. Dustin Rubinstein,

and Mariana F. Wolfner � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �21

Using Geographic Information Systems and Decision Support Systemsfor the Prediction, Prevention, and Control of Vector-Borne DiseasesLars Eisen and Rebecca J. Eisen � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �41

Salivary Gland Hypertrophy Viruses: A Novel Group of InsectPathogenic VirusesVerena-Ulrike Lietze, Adly M.M. Abd-Alla, Marc J.B. Vreysen,

Christopher J. Geden, and Drion G. Boucias � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �63

Insect-Resistant Genetically Modified Rice in China: From Researchto CommercializationMao Chen, Anthony Shelton, and Gong-yin Ye � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �81

Energetics of Insect DiapauseDaniel A. Hahn and David L. Denlinger � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 103

Arthropods of Medicoveterinary Importance in ZoosPeter H. Adler, Holly C. Tuten, and Mark P. Nelder � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 123

Climate Change and Evolutionary Adaptations at Species’Range MarginsJane K. Hill, Hannah M. Griffiths, and Chris D. Thomas � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 143

Ecological Role of Volatiles Produced by Plants in Responseto Damage by Herbivorous InsectsJ. Daniel Hare � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 161

Native and Exotic Pests of Eucalyptus: A Worldwide PerspectiveTimothy D. Paine, Martin J. Steinbauer, and Simon A. Lawson � � � � � � � � � � � � � � � � � � � � � � � � 181

vii

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EN56-Frontmatter ARI 28 October 2010 7:29

Urticating Hairs in Arthropods: Their Nature and Medical SignificanceAndrea Battisti, Goran Holm, Bengt Fagrell, and Stig Larsson � � � � � � � � � � � � � � � � � � � � � � � � � � 203

The Alfalfa Leafcutting Bee, Megachile rotundata: The World’s MostIntensively Managed Solitary BeeTheresa L. Pitts-Singer and James H. Cane � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 221

Vision and Visual Navigation in Nocturnal InsectsEric Warrant and Marie Dacke � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 239

The Role of Phytopathogenicity in Bark Beetle–Fungal Symbioses:A Challenge to the Classic ParadigmDiana L. Six and Michael J. Wingfield � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 255

Robert F. Denno (1945–2008): Insect Ecologist ExtraordinaireMicky D. Eubanks, Michael J. Raupp, and Deborah L. Finke � � � � � � � � � � � � � � � � � � � � � � � � � � � 273

The Role of Resources and Risks in Regulating Wild Bee PopulationsT’ai H. Roulston and Karen Goodell � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 293

Venom Proteins from Endoparasitoid Wasps and Their Rolein Host-Parasite InteractionsSassan Asgari and David B. Rivers � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 313

Recent Insights from Radar Studies of Insect FlightJason W. Chapman, V. Alistair Drake, and Don R. Reynolds � � � � � � � � � � � � � � � � � � � � � � � � � � � 337

Arthropod-Borne Diseases Associated with Political and Social DisorderPhilippe Brouqui � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 357

Ecology and Management of the Soybean Aphid in North AmericaDavid W. Ragsdale, Douglas A. Landis, Jacques Brodeur, George E. Heimpel,

and Nicolas Desneux � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 375

A Roadmap for Bridging Basic and Applied Researchin Forensic EntomologyJ.K. Tomberlin, R. Mohr, M.E. Benbow, A.M. Tarone, and S. VanLaerhoven � � � � � � � � 401

Visual Cognition in Social InsectsAurore Avargues-Weber, Nina Deisig, and Martin Giurfa � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 423

Evolution of Sexual Dimorphism in the LepidopteraCerisse E. Allen, Bas J. Zwaan, and Paul M. Brakefield � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 445

Forest Habitat Conservation in Africa Using Commercially ImportantInsectsSuresh Kumar Raina, Esther Kioko, Ole Zethner, and Susie Wren � � � � � � � � � � � � � � � � � � � � � � 465

Systematics and Evolution of Heteroptera: 25 Years of ProgressChristiane Weirauch and Randall T. Schuh � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 487

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Energetics of Insect Diapause

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