Feeding: Motivated Behavior in a Social Context Graham Redgrave, MD Johns Hopkins University School...

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Feeding: Motivated Behavior in a Feeding: Motivated Behavior in a Social ContextSocial Context

Graham Redgrave, MD

Johns Hopkins University School of Medicine

Department of Psychiatry and Behavioral Sciences

ObjectivesObjectives

• Recognize what it means for eating to be a “motivated” behavior

• Identify embodied elements governing feeding behavior in brain and gut

• Identify external factors influencing eating behavior

Motivated BehaviorsMotivated Behaviors

• Drive toward some goal

• Stereotyped behaviors satiate the drive

• Satiation is always temporary, giving rise to a behavioral cycle

• Cycle may be modulated by internal and external factors (e.g., illness, food availability)

• Learning takes place over time, with repeated iteration through the cycle

What is Drive?What is Drive?

• A construct, the element of the behavioral model that provides the “motive force,” hence “motivated behaviors”

• Embodied in multiple physiological control mechanisms

• The drive to eat serves the organism’s energy homeostasis

• In order to ensure repetitive feeding, the act is rewarding (hedonic)

HomeostasisHomeostasis

• Maintenance of a stable internal state despite changing environment (e.g., body temperature in mammals)

Cycle of Feeding BehaviorsCycle of Feeding Behaviors

hunger

foodacquisition

food consumption

satiety

meal patterns- frequency/timing- size- content- social context

satiety signals

meal initiation signals

learning

GI physiology

long-term homeostatic signals

pathways & transmitterssatiety signals

long-term homeostatic signals

pathways & transmitters

meal initiation signals

Smith, 2000

Control of Feeding is OverdeterminedControl of Feeding is Overdetermined

CorticotrophinReleasing Hormone

Bombesin

Peptide YY(3-36)

Insulin

Growth HormoneReleasing Hormone

Endorphin

Neuropeptide Y

Decrease IntakeIncrease IntakeLeptinGhrelin

Glucagon-likePeptide-1

Orexins

Serotonin

Norepinephrine

MelanocyteStimulating Hormone

Norepinephrine

MelanocyteStimulating Hormone

DopamineDopamine

CholecystokininGalanin

PancreaticPolypeptide

Agouti-RelatedProtein

CCK is a Prototypic Peripheral CCK is a Prototypic Peripheral Satiety SignalSatiety Signal

• Peptide released from gastric and duodenal mucosa into blood and surrounding tissue when stimulated by food in the enteric lumen

• Plasma level peaks 10-30 min after meal initiation and gradually subsides over 3-5 h

• CCK receptors in the vagus nerve allow communication with central satiety centers via the brainstem

• CCK also functions as a central neurotransmitter in multiple brain regions

Moran & Kinzig, 2004

CCK-A CCK-A Receptor Receptor Antagonism Antagonism Increases Increases Food IntakeFood Intake

CCK is a satiety signal, so blockade of its receptor should, and does, increase food intake.

Hunger Signals: GhrelinHunger Signals: Ghrelin

• Neuropeptide synthesized in the stomach

• Levels increase in food deprivation, peak prior to meals

• Receptors in the arcuate and ventromedial hypothalamus

Cummings et al., 2002

Ghrelin Peaks Ghrelin Peaks Before Meals, Before Meals, Levels Levels Increase After Increase After Weight LossWeight Loss

Saper, Chou, & Elmquist, 2002

Embodiment of Feeding Drives in Embodiment of Feeding Drives in the CNS: Big Picturethe CNS: Big Picture

PeripheryPeriphery

HypothalamusHypothalamus

BrainstemBrainstemRewardRewardCentersCenters

de Castro, 2000

Hedonic Hedonic Control: Control: Meal Size as Meal Size as A Function of A Function of Ratings of Ratings of Food Food Palatability Palatability And And Macronutrient Macronutrient ContentContent

Mechanisms of Hedonic Control Mechanisms of Hedonic Control of Feedingof Feeding

• The nucleus accumbens (NAc) is an important reward locus and contains multiple types of opioid receptors

• NAc receives input from feeding centers, such as the lateral hypothalamic area

• Opioid antagonists block food intake, particularly intake of sweet food

Levine et al., 1995

Opioid Antagonist Naloxone Blocks Opioid Antagonist Naloxone Blocks Intake of Sweet FoodIntake of Sweet Food

Homeostasis?Homeostasis?

• What can cause a population’s energy balance to shift?

hunger

acquisition

consumption

satiety

learning

Definition of ObesityDefinition of Obesity

• Body Mass Index (BMI)

–Weight (kg)/ Height (m2)

• Overweight: BMI > 25

• Obese: BMI >30

Obesity Trends* Among U.S. AdultsBRFSS, 1985

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Source: Behavioral Risk Factor Surveillance System, CDC.

No Data <10% 10%–14%

No Data <10% 10%–14% 15%–19%

No Data <10% 10%–14% 15%–19% ≥20%

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Contributions to Increased Obesity Contributions to Increased Obesity PrevalencePrevalence

• Increased energy intake

• Decreased energy expenditure

Increased Energy IntakeIncreased Energy Intake

• Portion size – “Supersizing”

• Availability of cheap, high calorie prepared foods, particularly those using high-fructose corn syrup

In Defense of HomeostasisIn Defense of Homeostasis

• Homeostasis is said to be “defended” against perturbation

• Observation or manipulation of the environment can demonstrate what is being defended

Spiegel et al., 1993

Meal Size is Meal Size is Defended in Defended in HumansHumans

Top panel: ingestion of small pieces of sandwich results in slower ingestion of calories.

Middle panel: subjects eating smaller pieces of sandwich ate for longer.

Bottom panel: there are no differences between consumers of small or large pieces of sandwich in terms of total calories consumed.

B Rolls et al, 2006

Energy Intake is Energy Intake is NotNot Defended in the Defended in the Presence of Increased Portion SizePresence of Increased Portion Size

Elliott et al, 2002

Annual Per Capita Use of Annual Per Capita Use of SweetenersSweeteners

Teff et al., 2004

Fructose Less Effective At Fructose Less Effective At Reducing Subsequent IntakeReducing Subsequent Intake

Barbie: www.flickr.com/photos/thomashawk/214495265/in/set-72157594491975505/; Report Card: NYT 12/0/07

Highly Energy Dense Food is Highly Energy Dense Food is Everywhere in the Culture!Everywhere in the Culture!

Bjursell et al., 2008

Decreased Locomotor Activity in Decreased Locomotor Activity in Response to a Western DietResponse to a Western Diet

ReviewReview• Homer eats to maintain energy homeostasis• When he eats, a complex, overdetermined

system of physiological elements drive Homer’s behavior

• Homer eats donuts because they taste good, are high in high-fructose corn syrup and do not satiate his appetite, and are cheap and available everywhere…

• …finally, when Homer eats his donuts, he may be less likely to go run around the track at Springfield High….

AcknowledgmentsAcknowledgments

• Paul McHugh, MD• MBU Rounds

• Contact: gwr@jhmi.edu• Website: http://jhedjournalclub.pbwiki.com

Eating Disorders Research Group

• Tim Moran, PhD

• Angela Guarda, MD

• Janelle Coughlin, PhD

• Ellen Ladenheim, PhD

• Shauna Reinblatt, MD

• Nick Bello, PhD

Feeding: Motivated Behavior in a Social Context Graham Redgrave, MD Johns Hopkins University School...

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