Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Metabolic Syndrome and Adipose Tissue

Yuji Matsuzawa, MD, PhDDirector and Professor Emeritus

Osaka University, Sumitomo Hospital, Osaka, Japan

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

A Novel Technique for the Determination of Body Fat by Computed Tomography

From Tokunaga K et al. Int J Obes 1983; 7: 437-45Reproduced with permission

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Visceral Fat Accumulation is an Important Determinant of Metabolic and Cardiovascular Disease

Insulin Resistance

Type 2 DiabetesDyslipidemia

Left VentricularDysfunctionYamashita S et al.

Diabetes Care 1996; 19: 287-91

Fujioka S et al. Metabolism 1987; 36: 54-9

Nakajima T et al. Am J Cardiol 1989; 64: 369-73

Kanai H et al. Hypertension 1990; 16: 484-90Kanai H et al. Hypertension 1996; 27: 125-9

Hypertension

Coronary Artery Disease

Sleep Apnea Syndrome

Nakamura T et al. Int J Obes Relat Metab Disord 1997; 21: 580-6Nakamura T et al. Atherosclerosis 1994; 107: 239-46

Shinohara E et al. J Intern Med 1997; 241: 11-8

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Visceral Fat

Subcutaneous Fat

Rib

os

om

al

pro

tein

s

Sec

reto

ryp

rote

ins

Cyt

op

lasm

ic

pro

tein

s

Nu

clea

r p

rote

ins

Mem

bra

ne

pro

tein

s

Cyt

os

kele

ton

pro

tein

s

Sig

nal

tran

sdu

ctio

n

En

erg

yp

rod

uct

ion

Mit

och

on

dri

alp

rote

ins

Growth factorsCytokinesComplement factorsetc.

30

20

10

0Fre

qu

en

cy (

%)

30

20

10

0

Fre

qu

en

cy (

%)

Gene Expression Profile of Human Adipose Tissue

Adapted from Matsuzawa Y et al. Arterioscler Thromb Vasc Biol 2004; 24: 29-33Reproduced with permission

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Enhanced Expression of PAI-1 in Visceral Fat

From Shimomura I et al. Nat Med 1996; 2: 800-3Reproduced with permission

PAI-1: plasminogen activator inhibitor-1

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Decreased Plasma Adiponectin in Visceral Obesity

80

60

0 100 200 300

Plasma PAI-1

40

20

0

Visceral Fat Area (cm2)

ng/ml

0 100 200

Visceral Fat Area (cm2)

20

0

5

10

15

g/ml

Plasma adiponectin

300

PAI-1: plasminogen activator inhibitor-1

Adapted from Matsuzawa Y et al.Arterioscler Thromb Vasc Biol 2004; 24: 29-33

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Plasma Adiponectin Levels

Relative Risk

Low High

1.0

2.1

Case-Control Study(CAD prevalence)

Adiponectin, an Independent Risk Factor of Coronary Artery Disease (CAD)

Adapted from Pischon T et al. JAMA 2004; 291: 1730-7

1.0

0.7

Relative Risk

Low High

Prospective Study(myocardial infarction

development)

Adapted from Kumada M et al. Arterioscler Thromb Vasc Biol 2003; 23: 85-9

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Effect of Adiponectin on Vascular Cells

0

1

2

3

4

5

Adiponectin

NF-B

VC

AM

-1

mR

NA

0

1

2

3

4

p-ERK

Cel

l P

rolif

erat

ion

PDGF-BB 10 ng/ml

0

50

100

Scavenger Receptor

Cho

lest

eryl

E

ster

(%

)

EndothelialCells

SmoothMuscle Cells

Macrophages

- + - + - +

VCAM-1: vascular cell adhesion molecule-1NF-B: nuclear transcription factor-Bp-ERK: p-extracellular signal-related kinasePDGF-BB: platelet-derived growth factor-BB

Adiponectin Adiponectin

Adapted from Ouchi N et al. Circulation 2000; 102: 1296-301

Adapted from Arita Y et al. Circulation 2002; 105: 2893-8

Adapted from Ouchi N et al. Circulation 2001; 103: 1057-63

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Endothelial Cells

Adipose Tissue

SmoothMuscle Cells

Mechanisms of Anti-atherogenicity of Adiponectin

Adapted from Matsuzawa Y et al. Arterioscler Thromb Vasc Biol 2004; 24: 29-33

Adhesion Molecules

Plaque Rupture

Macrophages

v

v

v

Adiponectin

TIMP-1

TNF-HB-EGF

Monocyte

TNF-: tumor necrosis factor-TIMP-1: tissue inhibitor of metalloproteinase-1HB-EGF: heparin-binding EGF-like growth factor

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Hypo-adiponectinemia

Visceral Fat Accumulation

GeneticVariations

Type 2 Diabetes

Hypertension

Atherosclerosis

Cardiac Dysfunction

Non-alcoholic steatohepatitis

Cancers

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

www.cardiometabolic-risk.org