Adipose Tissue, Inflammation, and Atherosclerosis

Harald ManggeDepartment of Laboratory Medicine

Medical University of Graz, Austria

BackgroundObesity a global epidemic

The rate of obesity in China has increased by

97% in 10 years, according to a

government report.

Also in

Asia

Obesity Sequels

MI Stroke

HypertensionFatty Liver

postoperative complications

e.g.Sepsis

Type IIDiabetes

Athero-sclerosis

ArthrosisReflux, Infertility

Congenital Defects

Overweight/Obesity

CancerGut, Prostate,

Breast, Renal, LiverEsophagusMelanoma

inflammation

?Cirrhosis, HCC

1975: 1,4 pro 100.000 2006: 3,9 pro 100.000

AtherosclerosisA major burden of obesity

Early beginning

increased IMT

Endstage

Lifelong disease

„Lifestyle“

„fatty streaks“

Chronic immune mediated inflammation

Stroke

0 10 20 30 40 50 60 70 yrs

Clinical endpoints

Chronic vascular inflammation

Immune system

Adipokines SAT Distribution

Obesity

Obesity and AtherosclerosisA complex interaction

Oreopoulos, A. et al. Eur Heart J 2009 30:2584-2592; doi:10.1093/eurheartj/ehp288

The “Obesity Paradox“

BMI < 18.5

BMI = 18.5-24.9

Irrespective of treatment strategy, obese have lower mortality compared to lean patients

Kaplan-Meier survival in patients with established coronary artery disease (CAD)

Ris

k o

f m

ort

alit

y (%

)

Body-Mass-Index

0

50

100

150

200

250

300

I II III

15 18,5 25 30 35 40

Obesity

Despite “Obesity Paradox“Obesity is life-threatening

HypertensionFatty Liver

Type IIDiabetes

Athero-sclerosis

SepsisICU,

Surgery

Cancer

Inflammation

?

• Better outcome in cases of CAD andincreased Mortality in Obesity – a contradiction?

• Answers may be given by the complex function of the adipose tissue.

Lean Obese

Adipose tissueInflammed in obesity

Inflammation

modified fromTilg H., Moschen A.:

Nature Review Immunology, 6:772-83, 2006

lean obese

Proinflammatoryadipokine-cytokine“cocktail“

-++

+++ CCL2 = MCP1

++

IL-6, a principal offender

The Adipose TissueAn Immune / Endocrine Organ

Endocrine activities of adipocytes

adipocyte

Leptin*Eating habits

Resistin, Visfatin

Typ II Diabetes

TNF-aInflammation

IL-6Inflammation

Adiponectin*Vasoprotection

MCP-1(CCL2)Inflammation,

Monocytes

Plasminogen activatorinhibitor (PAI-1)

Clotting

AngiotensinogenBlood pressure

antiinflammatory

proinflammatory

proinflammatory

proinflammatory

proinflammatory

*most abundant adipokines

AdiponectinThree subfractions

High Molecular Weight (HMW)Adiponectin oligomer

Medium Molecular Weight (MMW) Adiponectin hexamer

Low Molecular Weight (LMW)Adiponectin trimer

globular domain

collagenous domain

Oligomerisation

Source

atheroprotective

Monocyte adherence

inflammation

AdiponectinEffects on monocyte adherence

monocytesCXC3CR1hiCCR2−

Ly6ClowCD14lowCD16+

MCP, M-CSF CD40L

TNFa, IL-1, TGFß, MMPs, PDGF, IGF

oxLDL

cell injury byoxLDL, diabetes, infection,

smoking, oxidative stress etc.

Th1-cellsIFNg TNF

TGFß IL-17

monocytesCXC3CR1lowCCR2+

Ly6ChiCD14+CD16−

TNFa, IL-1, TGFß, MMPs, PDGF, IGF-1, MCP-1

Influence of cytokine polymorphisms

+/- +/-

smooth muscle cellsHLA-DR CD40L

AG-presentation proliferation

T-cellsTh1 / Th2

IL-12 IL-18 IL-10

plateletsRANTES

Altered immune reactivity

endothelial cellsICAM, VCAM CCR2, CD40LIL-8, MCP-1

Fractalkin/CX3CR1 PDGF, Selectins

+

+

+

Initiation

Perpetuation

IL-4 ?

?

IL-10?

Local aggravation of arteritis

Acceleratedlesion formation

Complicated lesion

Normal artery Arteritis

RegressionFatty streak

Vicious circle ofinflammation, lipiddeposition, and furtherinflammation

FractalkinRANTESGM-CSFM-CSF

RRrTT

CRP

+

+

PPARsNeopterin

inhibition byß-blockers e.g.

carvedilol, nebivolol

Inhibition byadiponectin

Immmune activation in early and advanced Atherosclerosis

Mangge et al. Clin Chem Lab Med. 42:467-74, 2004 Mangge, Almer et al. Current Medicinal Chemistry, 17:4511-20. 2010

Visceral adipose tissue (VAT)Center of the immune-mediated inflammation

Libby et al Circulation Journal 74:213-220, 2010

LFLow fat diet

HFHigh fat diet

LF HF

Abbr.: CD11c, F4/80, macrophage-, CD3, CD4/8 Tcell-,B220, B-cell-markers.

Balkau et al. Circulation. 2007 October; 116(17): 1942–1951.

Visceral adipose tissue (VAT)Major responsible for CVD (also in lean people)

CVD (cardiovascular disease)Diabetes

CVD (cardiovascular disease)Diabetes

CVD CVD

Obesity research in Graz

STYJOBS / EDECTA Cohort

http://www.meduni-graz.at/styjobs/http://clinicaltrials.gov/ct2/show/NCT00482924

EDECTASTYJOBS

DatabaseBiobank

0 5 10 15 20 25 30 35 40 55 yrs

preclinical Diagnosis (Theragnosis)new individual Risk profiles, Genetics

Early Intervention (nutrition?)

STYrian Juvenile OBesity Study

Public Health

SystemsBiology

LifestyleAging

IT Net-working

Atherosclerosis

PredictionPersonalisation

PreventionLipometry Adipokines Inflammation

Craving Brown / White Adipose Tissue

A body mass index spectrum from 10 to 50 kg/m2from anorexia to morbid adiposity

Early Detection of Atherosclerosis

Lipometry(SAT-TOP)

Complex Database(>200 variables / proband)

Prospective end size n=1600

Bioresource

Biomarkers,Adipokines

Lipids, oxLDLInsulin, conLab

STYJOBS / EDECTAA large set of clinical, anthropometric, laboratory data

Carotissono-graphy (IMT)

0 10 20 30 40 50 60 70 80 years

Complex anthropometry: SAT-Distribution by lipometry

Lipometry

SAT thickness by infrared methodPatent EP2091415

STYJOBS / EDECTAFocus of research I

AdipokinesLow grade inflammation, atherosclerosis, metabolic syndrom, fatty liver, oxStress, craving

adipocyte

Leptin*Eating habits

Resistin, Visfatin

Typ II Diabetes

TNF-aInflammation

IL-6Inflammation

Adiponectin*Vasoprotection

MCP-1(CCL2)Inflammation,

Monocytes

Plasminogen activatorinhibitor (PAI-1)

Clotting

AngiotensinogenBlood pressure

STYJOBS / EDECTAFocus of research II

Wissenschaft und Forschung

Zukunftsfonds

Recent Data

STYJOBS / EDECTA

STYJOBS / EDECTAResults – age range overview, sets of variables

Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, 2010 PMID: 18846045

Variables Clinical/Anthropometric/Carotis-sono (82)

Laboratory/Biomarkers/Adipokines (100)Glucose metabolism, liver, kidney function, lipids, oxidative/nitrosative stress, adipokines, orphane vascular markers, clotting

Genetic/mitochondrial function/miscellaneous (100)

PatientsN=890

IntendedN=1500

STYJOBS / EDECTAResults, vascular/inflammatory/metabolic markers

Adiponectin

US-CRPCarotis IMT

syst Bloodpressure HOMA-index

Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, 2010 PMID: 18846045

R=0.25P<0.01

R=0.34P<0.01

R=0.29P<0.01

R=0.58P<0.01

R=0.48P<0.01

(-) (+)

Interleukin-6R=0.33P<0.01

BMI(-) (+)

STYJOBS / ResultsUltrasonography of CCA Intima Media Thickness (IMT)*

p < 0.001

,03

,04

,05

,06

,07

,08

,09

,1

,11

A. c

aro

tis

com

mu

nis

IMT

cm

Overweight/obese (n=370)Controls (n=153)

13y

IMT

Mangge et al Exp Clin Endocrinol Diabetes. 2004.PMID: 1523902Mangge et al Atherosclerosis 2008, PMID: 18656877 Mangge et al Obesity 2009, PMID: 18846045

STYJOBS, age below 18 years, n=523

STYJOBS/ResultsIMTUS-CRP (Inflammation)

p <0.001

weak correlation

R=0.18

STYJOBS, age < 18 years

STYJOBS / ResultsIMT versus waist

Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity Research 2008, PMID: 18846045

Excellent correlation

Waist circumference vs Carotis IMT

R=0.5

STYJOBSage < 18 years

Visceral adipose tissue (VAT)Center of the immune-mediated inflammation

Libby et al Circulation Journal 74:213-220, 2010

LFLow fat diet

HFHigh fat diet

LF HF

Abbr.: CD11c, F4/80, macrophage-, CD3, CD4/8 Tcell-,B220, B-cell-markers.

STYJOBS / ResultsIntima media thickness versus transaminases

Mangge et al Exp Clin Endocrinol Diabetes. 2004.PMID: 1523902Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, PMID: 18846045

STYJOBS, age < 20 years, n=523

***

r=0.37p<0.01

STYJOBS / EDECTA

Lipometry

SAT thickness by infrared methodPatent EP2091415

STYJOBS / ResultsIMT versus Anthropometry

Multiple Regression includingBMI, %bodyfat, waist, hip, waist to height ratio, lipo measure points 1-15, Adiponectin subfractions

Multiple Regression includingBMI, %bodyfat, waist, hip, waist to height ratio, lipo measure points 1-15

Preis SR, Massaro JM, Hoffmann U, D'Agostino RB

Sr, Levy D, Robins SJ, Meigs JB, Vasan RS, O'Donnell CJ, Fox CS.

Neck circumference as a novel measure of cardiometabolic risk: the Framingham Heart study.

Neck circumference is associated with CVD risk factors even after adjustment for VAT and BMI. These findings suggest that upper-body sc fat may be a unique, pathogenic fat depot.

J Clin Endocrinol Metab. 2010 Aug;95(8):3701-10. Epub 2010 May 19.

STYJOBS / ResultsHMW, MMW, LMW / total adiponectin ratios

HMW / total adiponectin

MMW / total adiponectin

LMW / total adiponectin

Mangge et al. Preatherosclerosis and adiponectin subfractions in obese adolescents. Obesity, 2008, PMID:18846045Nuchal thickness of subcutaneous adipose tissue is tightly associated

with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis, 2009, PMID:18656877

High Molecular Weight (HMW)

adiponectin oligomer

Medium Molecular Weight(MMW)

adiponectin hexamer

Low Molecular Weight (LMW)

adiponectin trimer

Oligomerisation disturbed ?

STYJOBS / ResultsAdiponectin

HDL-cholesterol is

HMW Adiponectin decrease is closely associated with

increased carotis IMT

Mangge et al. Preatherosclerosis and adiponectin subfractions in obese adolescents. Obesity, 2008, PMID:18846045Nuchal thickness of subcutaneous adipose tissue is tightly associated

with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis, 2009, PMID:18656877

Results of a multiple regression

HDL-cholesterol is

LMW Adiponectin increaseis closely associated with

nuchal fat thickness

Results of a multiple regression

Szmitko et alAm J Physiol Heart Circ Physiol 292: 1655-1663, 2007.

Adiponectin HMW fraction most effective against AS

STYJOBS / ResultsOxidative stress, oxidative LDL

HDL-cholesterol is HDL cholesterol is the best predictor for lipid peroxidation irrespective of age, gender, and

other biomarkers

Mangge et al. High density lipoprotein cholesterol level is a robust predictor of lipid peroxidationirrespective of gender, age, obesity, and inflammatory or metabolic biomarkers

ClinicaChimActa, 2011, in press

Results of the multiple regression

STYJOBS / EDECTAResults - Cardiovascular risk pattern

with emphasis on BMI, Age, Gender

Age(-) (+)

Carotis IMT Systolic BP Diastolic BP

STYJOBS / EDECTAResults - Hepatic risk patternwith emphasis on BMI, Age, Gender

Age(-) (+)

Cholinesterase ALT/GPT gammaGT

ALT/GPT cut offFemale adult <40 U/L, <15years < 25 Male adult <30, <15years < 25

STYJOBS / EDECTA

Results

Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2009, PMID: 18846045Mangge et al Current Med Chem, 2010 PMID:21062254

Consider earlydevelopment of gender

related risk profiles!

STYJOBS / EDECTA - ResultsSummary

HMW adiponectin is decreased in the early phase of vascular abnormalities in obesity.

As the LMW subfraction is increased, and the HMW subfraction decreased, the oligomerisation from LMW to HMW adiponectin may be disturbed.

Trunk weighted obesity is associated with very low HMW adiponectin, and stronger increased carotis IMT.

HDL cholesterol decrease is the best predictor for lipid peroxidation.

Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity Research 2008, PMID: 18846045

General conclusion

Obesity is a chronic inflammatory disease.

Irrespective of sex, age and gender, the inflammatory activation associated with abdominal fat accumulation is crucial for obesity related sequels like atherosclerosis.

Adipokines are centrally involved in the chronic inflammation of obesity. The balancebetween the most abundant adipokines , adiponectin and leptin may be crucial for the clinical course of atherosclerosis.

The “obesity paradox” may be explained by “protective” antiinflammatory qualities of the adipose tissue. However, abdominal (trunk) obesity abrogates the protective effects.

Therapeutic modification of chronic low grade inflammation with reference to the individual SAT distribution may become an important challenge for the future.

STYJOBS / ResultsConclusion

Our data show that already the early phase of obesity is associated with chronic

inflammation, preatherosclerosis, and an essentially altered adipokine synthesis.

SAT- distribution (visceral, nuchal) is a crucial risk factor.

Pilz S, Mangge H et al. J of Clin Endocrinology and Metabolism, PMID: 15928248, 2005Moeller R, Mangge H et al. Obesity, PMID: 17495209, 2007

Gruber H, Mangge H et al. Int J of Obesity PMID: 18656877, 2008Mangge et al. Atherosclerosis, PMID: 18656877, 2009

Mangge et al. Obesity, PMID: 18846045, 2009Wallner, Mangge et al, PMID:20168310, 2010

Mangge et al Current Med Chem, PMID:21062254, 2010Fritsch, Mangge et al Atherosclerosis, PMID:21334626, 2011

Mangge, Renner et al, PMID:21318054, 2011Mangge et al ClinChimActa, 2011, in press

http://www.meduni-graz.at/styjobs/http://clinicaltrials.gov/ct2/show/NCT00482924

Thank you for the attention!

Libby et al Circulation Journal 74:213-220, 2010

JUPITER-Trial

SubjectsNo history of CAD

LDL-cholesterol <3.4mmol/L

CRP > 19.0nmol/L

Random treatment

Rosuvastatin 20mg daily or

Placebo

STYJOBS / EDECTALeptin

Leptin R=0.68P<0.01N=804

STYJOBS / EDECTAUric acid, HDL-cholesterol…vs BMI

BMI

Uric acid HDL-cholesterol ox-LDL

BMI mother BMI fatherLDL-cholesterol

Mangge et al Atherosclerosis 2009, PMID: 18656877

Mangge et al Obesity 2008, PMID: 18846045

R=0.5 R=0.28 R=0.19

n.s. R=0.38 R=0.29

Juvenile ObesityReduces life expectancy

Franks PW et al. Childhood Obesity, Other Cardiovascular Risk Factors, and Premature

Death. N Engl J Med. 11; 362:485-493, 2010

Childhood obesity is associated with premature death in adulthood

Followed,

obese children

(american

indians),

not suffering

from diabetes.

Early ObesityFactors associated with premature death from endogenous causes

Childhood hypertension was strongly associated with the rate of death from endogenous causes

in early adulthood (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24).

No significant associations were observed between death rates and childhood cholesterol levels*.

*Franks PW et al. Childhood Obesity, Other Cardiovascular Risk Factors, and Premature

Death. N Engl J Med. 11; 362:485-493, 2010

STYJOBS age<20y

R = 0.5

P<0.01

R =-0.5

P<0.01

n.s.

Future activities

Epigenetics, miRNAs and white/brown AT, Fatty Liver Disease ↔ Nutrition, Modulation of Craving

internet

http://clinicaltrials.gov/ct2/show/NCT00482924

http://www.meduni -graz.at/styjobsFrom 1 st

decade

From 2 nd

decade

From 3 rd

decade

Tackling the early burden in obesity

From 1 st

decade

From 2 nd

decade

From 3 rd

decade

Tackling the early burden in obesity

STYJOBS / EDECTAWhere we are at the moment870 probands recruited, 1500 intended

Human evolution – the shape of things to come?

Nuchal fat, White/Brown AT, Vascular Risk, Adipokines Hippocampus, Craving, Insulin, SAT distribution

STYJOBS / EDECTAScope of recent publications

Stelzer, Mangge et al. Clinical Chemistry, submitted 2011 Focus Clotting, IL-6, InflammationRaggam, Prüller, Mangge et al. Obesity, submitted 2011 Focus ClottingZelzer, Mangge et al. Clinica Chimica Acta, in press, 2011 Focus Biomarkers (oxLDL) Mangge, Almer, Renner et al. Journal of Obesity, PMID: 21318054, 2011 Focus Genetics (FTO Gen), SAT-TopographyMangge, Fuchs et al. Journal of Obesity, PMID: 21274279 2011 Focus Biomarkers (Neopterin)Arnold, Mangge, Strobl et al. Pediatric Research, PMID: 21135756, 2011 Focus Biomarkers (Clusterin)Mangge, Fuchs et al. Current Medicinal Chemistry, PMID: 21062254, 2010Focus Atherosclerosis (Inflammation, AT)Fritsch, Mangge et al. Atherosclerosis PMID: 20619835, 2010 Focus Clotting (ETP, procoagulant PPLs)Wallner-Liebmann, Mangge et al. Obesity PMID: 20168310, 2010 Focus Craving (Insulin, Hippocampus)Mangge et al. Atherosclerosis, PMID: 18656877, 2009 Focus Biomarkers (Adiponectin)Mangge et al. Obesity, PMID: 18846045, 2009 Focus Adiponectin (SAT Topography)Gruber H, Mangge H et al. Int J of Obesity PMID: 18656877, 2008 Focus Atherosclerosis (Oxidative“Stress”)Mangge, Almer et al. Diabetes Care PMID: 18375422, 2008 Focus Insulin resistance (Metabolism)Truschnig, Mangge et al. Exp and Clin Endocrinol & Diabetes, PMID: 18072008, 2008 Focus Atherosclerosis (Food Allergy)Moeller, Mangge et al. Obesity, PMID: 17495209, 2007 Focus Atherosclerosis (SAT Topography)Pilz, Mangge et al. J of Clin Endocrinology and Metabolism, PMID: 15928248, 2005 Focus Atherosclerosis (Adiponectin)Mangge et al. Exp and Clin Endocrinology & Diabetes, PMID: 15239023, 2004 Focus Atherosclerosis (Inflammation)

STYJOBS / EDECTAFocus interdisciplinarity

PartnersMedical-, Karl Franzens-, Technical-Universities of Graz

Gunter Almer, Verena Biedermann, Andreas Meinitzer, Florian Freytag, Renate Horejsi, Reinhard Möller, Clemens Diwoki, Wolfgang Schnedl, Kerstin Hingerl, Karl Koschutnig, Gernot Reishofer, Renate Kruschitz, Barbara Blaschitz, Matthias Saba-Lepek, Marcel Scheideler, Robert Gasser,

Elisabeth Kraigher-Krainer, Martie Truschnig-Wilders, Sieglinde Zelzer, BioNanoNet, Peter Opriessnig, Ruth Prassl, Paul Debagge, Peter Hofmeister, Rudolf Stollberger, Andreas Zimmer, FattyLiverResearch Consortium, Sandra Wallner-Liebmann, Caroline Lackner, Johannes

Haybäck, Peter Abuja, Rudolf Stauber, Rottraud Ille, Harald Mangge

ExternalParacelsus Privatuniversität Salzburg

Walter Sperl, Daniel Weghuber, Friedrich Hoppichler, intended cooperation with the

University of MunichReinhard Halle, Sportsmedicine

Boston University School of Medicine, Framingham Vasan S. Ramachandran

Wissenschaft und ForschungZukunftsfonds

STYJOBS / ResultsInterleukin-6

Mangge et al. Chronic inflammation in obesity:

Fibrinogen is an independent predictor for interleukin-6 in juveniles and adults ClinicalChemistry, 2011, submitted

Fibrinogen is the best predictor for Interleukin-6 irrespective of age, gender, and other biomarkers

Results of the multiple regression

Carotid intima-media thickening indicates a higher vascular risk across a wide age

range: prospective data from the Carotid Atherosclerosis Progression Study (CAPS).

Lorenz et al. Stroke, 2006

"Its predicitive value is as high in younger subjects as in older subjects"

IMT determination of CCAsResults of a recent study

STYJOBSResults

Metabolic Profiles

STYJOBS/ResultsBlood pressure

HO

MA

in

de

x20

15

10

5

0

p <0.0001

obesecontrol

sys

toli

c b

loo

d p

res

su

re (

mm

Hg

)

180

160

140

120

100

80

60

p <0.01

r = 0.5 p < 0.001

Mangge et al Atherosclerosis 2008, PMID: 18656877

Mangge et al Obesity Research 2008, in press

STYJOBSResults

Glucose metabolism

STYJOBS/ResultsGlucose metabolism

obesecontrols

HO

MA

in

de

x20

15

10

5

0

p <0.0001HOMA-Index =

FI x FGlu : 22,5

FI = fasting insulin

FGlu = fasting

glucoseGlucose mmol/L

Insulin uE/ml

HOMA IR =

homeostatic model

assessment - insulin

resistanceMangge et al,

Int J of Obesity,

2006, in press

STYJOBS/ResultsDiabetes

obesecontrols

HO

MA

in

de

x20

15

10

5

0

p <0.0001

HOMA-Index =

FI x FGlu : 22,5

FI = fasting insulin

FGlu = fasting

glucoseGlucose mmol/L

Insulin uE/ml

HOMA IR =

homeostatic model

assessment - insulin

resistance

Mangge et al

Atherosclerosis

2008, PMID:

18656877

Mangge et al

Obesity Research

2008, in press

STYJOBSResults

Liver function

STYJOBS/ResultsLiver enzymes I

p = 0.03 p < 0.0001

n.s. p < 0.0001

r = 0.35

STYJOBS/ResultsLiver enzymes II

p < 0.0001 p < 0.0001

p < 0.0001

r = 0.2

p < 0.0001

r = 0.24

STYJOBSResults

Lipids, Uric Acid,

Oxidative / Nitrosative “Stress”

STYJOBS/ResultsHDL-cholesterol, oxLDL

20

30

40

50

60

70

80

90

HD

L-C

ho

leste

rin

mg

/dl

controls obese

***

Mangge H, Pilz S. Journal of Clinical Endocrinology and Metabolism 2005

STYJOBS / ResultsLipid profile, and uric acid

p < 0.001 p < 0.0001 p < 0.001 p < 0.0001

Fatty acids Triglycerides VLDL-Cholesterol Uric acid

STYJOBS / ResultsTotal NO (NOX), oxLDL

Gruber H, Mangge H et al. International J Obesity, 32(5): 826-31, 2008 PMID: 18197180,

p < 0.001

(MannWithney)

Source, Libby et al Circulation Journal 74:213-220, 2010

MonocytesPrincipal offenders in atherogenesis

Obesity in EuropeAdults

Adults

BMI > 30 Source: IASO

International Obesity

TaskForce

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

Obesity in EuropeJuveniles

Kids

around 10 years*

> 30%

20 - 29.9%

10 - 19.9%

no data

Source: IASO

International Obesity TaskForce

modified from

Tilg H., Moschen A.:

Nature Review Immunology, 6:772-83, 2006

AdiponectinReceptors

Antiinflammatory effect

(mainly in liver)

(endothelial,

smooth muscle

cells)

↓ Oxidative stress

↓ Apoptosis

T-Cadherin

Okamoto, Y. et al. Circ Res 2008;102:218-225

IP-10, Mig, and I-TAC are expressed in M, endothelial cells, and

smooth muscle cells in vasculature. They recruit T-lymphocyte

migration, important for the development of atheromata

Adiponectin

Chemokine suppression

Inhibition of of CXCR3 chemokine ligand expression

Adiponectin reduces IP-10, Mig, and I-TAC mRNA levels in human M

Abbrevations

APN, Adiponectin

IP, INFg induced protein

Mig, Monokine induced by gINF

I-Tac, INF-inducible Tcell Alpha chemoattractant

Obesity in EuropeAdults

AdultsBMI > 30

Source: IASO International Obesity

TaskForce

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

Obesity in EuropeJuveniles

Kidsaround 10 years*

> 30%

20 - 29.9%

10 - 19.9%

no data

Source: IASO International Obesity TaskForce