22ππrrDr. Dr. FranFranççois Mach, MD,ois Mach, MD,Division de CardiologieDivision de Cardiologie
Hôpital Universitaire de GenHôpital Universitaire de Genèè[email protected]@medecine.unige.ch
www.cardiologywww.cardiology--geneva.chgeneva.ch
GenGenèèveve, HUG le 2 mars 20, HUG le 2 mars 200066
Colloque du Service de CardiologieColloque du Service de Cardiologie
Despite therapeutic advances, cardiovascular Despite therapeutic advances, cardiovascular disease remains the leading cause of death (USA)disease remains the leading cause of death (USA)
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% of all deaths% of all deaths(right axis)(right axis)
No. of deathsNo. of deaths(left axis)(left axis)
% A
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HeartHeartdiseasedisease andand
strokestroke
CancerCancer AccidentsAccidents ChronicChroniclowerlower resp.resp.
diseasedisease
DiabetesDiabetes
Am J CardiolAm J Cardiol 19981998;82(;82(supplsuppl 10A)10A)
AthAthéérogenrogenèèsese
Physiopathologie de lPhysiopathologie de l’’athathéérosclrosclééroserose
SmokingSmoking
EndothelialEndothelial DysfunctionDysfunctionAthAtheerorogenesisgenesis
DiabDiabeetetess
Oxydative StressOxydative StressOxydative Stress
HypertensionHypertension
High LHigh LDLDL--cholcholLowLow HDLHDL--cholchol
ObesityObesitySedentaritySedentarity
CardioVascularCardioVascular RiskRisk FactorsFactors
IntraIntra--abdominal obesity (adiposity)abdominal obesity (adiposity)
and cardiovascular risk factorsand cardiovascular risk factors
115 cm115 cm
2.3 mmol/l2.3 mmol/l
0.9 mmol/l0.9 mmol/l
6.8 mmol/l6.8 mmol/l
•• Obesity: BMI Obesity: BMI ≥≥ 30 (kg/m30 (kg/m22))7% of the world population of adults or about 312 7% of the world population of adults or about 312 millionmillion
•• Overweight: BMI 25Overweight: BMI 25--30 30 (kg/m(kg/m22))1.1 billion adults1.1 billion adults
•• Prevalence of obesity and overweight in childrenPrevalence of obesity and overweight in childrenas high as 36%as high as 36%
The Current Obesity PandemicThe Current Obesity Pandemic
WorldwideWorldwide epidemiaepidemia of of «« diabesitydiabesity »»
CardiovascularCardiovascular RiskRisk FactorsFactors
Obesity, Body Fat Distribution and Risk of CVD Obesity, Body Fat Distribution and Risk of CVD
N Engl J MedN Engl J Med 19981998;338:1;338:1
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adjusted risk of CHD, even after adjusting for BMI and other CVadjusted risk of CHD, even after adjusting for BMI and other CV risk factorsrisk factors
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JAMAJAMA 19981998;280:1843;280:1843
Quintiles of waist circumference (cm)Quintiles of waist circumference (cm)
Obesity, Body Fat Distribution and Risk of CVD Obesity, Body Fat Distribution and Risk of CVD
RR >3 foldRR >3 fold RR between 2RR between 2--3 fold3 fold RR between 1RR between 1--2 fold2 fold
Type 2 diabetesType 2 diabetes CVDCVD HPG axis abnormalitiesHPG axis abnormalities
Gallbladder diseaseGallbladder disease HypertensionHypertension CancerCancer
DyslipidemiaDyslipidemia Knee Knee osteoarthritesosteoarthrites Lower spine problemsLower spine problems
Sleep ApneaSleep Apnea GoutGout Birth defectsBirth defects
Adapted from WHO Report, Geneva Adapted from WHO Report, Geneva 19981998
Relative Risk of ObesityRelative Risk of Obesity--Associated Associated Health ProblemsHealth Problems
AbdominalAbdominalobesityobesity
DyslipidaemiaDyslipidaemiaHypertensionHypertension
Glucose intoleranceGlucose intoleranceInsulin resistanceInsulin resistance
Increased Increased CardiometabolicCardiometabolic RiskRisk
Multiple cardiovascular risk factors Multiple cardiovascular risk factors drive adverse clinical outcomesdrive adverse clinical outcomes
CARDIOVASCULAR DISEASECARDIOVASCULAR DISEASE
Classical Risk FactorsClassical Risk Factors Novel Risk FactorsNovel Risk Factors
Major Unmet Clinical NeedMajor Unmet Clinical Need
Metabolic syndromeMetabolic syndrome
AbdominalAbdominalObesityObesity
↓↓HDLHDL--CC
↑↑TGTG
↑↑TNFTNFαα ILIL--66
↑↑PAIPAI--11
↑↑GluGlu
↑↑InsulinInsulin
T2DMT2DM↑↑SmokingSmoking↑↑ LDLLDL--CC ↑↑ BPBP
Multiple cardiovascular risk factors Multiple cardiovascular risk factors drive adverse clinical outcomesdrive adverse clinical outcomes
•• High waist circumferenceHigh waist circumference
•• Plus any two ofPlus any two of
•• Triglycerides (Triglycerides (≥≥ 1.7 mmol/L [150 mg/dL])1.7 mmol/L [150 mg/dL])‡‡
•• HDL cholesterolHDL cholesterol‡‡
•• MenMen < 1.0 mmol/L (40 mg/dL)< 1.0 mmol/L (40 mg/dL)
•• WomenWomen < 1.3 mmol/L (50 mg/dL)< 1.3 mmol/L (50 mg/dL)
•• Blood pressure Blood pressure ≥≥ 130 / 130 / >>85 mm Hg85 mm Hg‡‡
•• FPG (FPG (≥≥ 5.6 mmol/L [100 mg/dL])5.6 mmol/L [100 mg/dL]), or diabetes, or diabetes
IDF criteria of the metabolic syndrome IDF criteria of the metabolic syndrome
Abdominal obesity: required for diagnosing the Abdominal obesity: required for diagnosing the metabolic syndromemetabolic syndrome
International Diabetes Federation (International Diabetes Federation (20052005))
‡‡or specific treatment for these conditionsor specific treatment for these conditions
Metabolic syndrome has a negative impact Metabolic syndrome has a negative impact on CV health and mortalityon CV health and mortality
DiabetologiaDiabetologia 20012001;44:1148;44:1148
No metabolic syndromeNo metabolic syndrome
00
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AllAll--cause cause mortalitymortality
Cardiovascular Cardiovascular mortalitymortality
Mor
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Mor
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**
*p<0.001*p<0.001
00
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Pre
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nce
(%
)P
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ce (
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*p<0.001*p<0.001
**
**
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Metabolic syndromeMetabolic syndrome
•• New IDF criteria:New IDF criteria:
NCEP NCEP 20022002; ; International Diabetes Federation International Diabetes Federation 20052005
•• Current NCEP ATPCurrent NCEP ATP--III criteriaIII criteria
>102 cm (>40 in) in men, >88 cm (>35 in) in women>102 cm (>40 in) in men, >88 cm (>35 in) in women
WomenWomenMenMen
>>90 cm (35.4 in)90 cm (35.4 in)
>>80 cm (31.5 in)80 cm (31.5 in)
>>80 cm (31.5 in)80 cm (31.5 in)
>>80 cm (31.5 in)80 cm (31.5 in)
>>85 cm (33.5 in)85 cm (33.5 in)
>>90 cm (35.4 in)90 cm (35.4 in)
>>90 cm (35.4 in)90 cm (35.4 in)
>>94 cm (37.0 in)94 cm (37.0 in)
JapaneseJapanese
ChineseChinese
South AsianSouth Asian
EuropidEuropid
Abdominal obesity and Abdominal obesity and waist circumference thresholdswaist circumference thresholds
Place a tape measure around the Place a tape measure around the bare abdomen, just above the hip bare abdomen, just above the hip bone bone
Be sure the tape is snug, but does Be sure the tape is snug, but does not compress the skin not compress the skin
The tape should be parallel to the The tape should be parallel to the floor floor
The patient should relax and The patient should relax and exhale while the measurement is exhale while the measurement is made made
http://http://win.niddk.nih.gov/publications/tools.htm#circumfwin.niddk.nih.gov/publications/tools.htm#circumf
Measuring waist circumference: Measuring waist circumference: a practical guide from the NIDDK/NIHa practical guide from the NIDDK/NIH
Am J CardiolAm J Cardiol 19941994;73:460;73:460
Waist circumference correlates closely Waist circumference correlates closely with intrawith intra--abdominal adiposityabdominal adiposity
IAA: the Perils of PortlinessIAA: the Perils of Portliness
Visceral fatVisceral fat
Subcutaneous fatSubcutaneous fat
J J MagnMagn ResonReson ImagingImaging 20052005;21:455;21:455
+ 18%+ 18%55.1%55.1%46.7%46.7%WomenWomen
+ 28%+ 28%36.9%36.9%29.5%29.5%MenMen
Relative Relative changechange
NHANES NHANES (1999(1999––2000)2000)
NHANES IIINHANES III(1988(1988––1994)1994)
ObesObes ResRes 20032003;11:1223;11:1223
US National Health andUS National Health andNutrition Examination Survey (NHANES)Nutrition Examination Survey (NHANES)
Abdominal obesity defined as waist circumference: >102 cm (>40 iAbdominal obesity defined as waist circumference: >102 cm (>40 in)n)in men or >88 cm (>35 in) in women in men or >88 cm (>35 in) in women
Growing prevalence of abdominal obesityGrowing prevalence of abdominal obesity
USUS 36.936.9 55.155.1 46.046.0
Spain Spain 30.530.5 37.837.8 34.734.7
ItalyItaly 24.024.0 37.037.0 31.531.5
UKUK 29.029.0 26.026.0 27.527.5
FranceFrance –– –– 26.326.3
NetherlandsNetherlands 14.814.8 21.121.1 18.218.2
Germany Germany 20.020.0 20.520.5 20.320.3
Men (%)Men (%) WomenWomen (%)(%) TotalTotal (%)(%)
High waist circumference: High waist circumference: >>102 cm (102 cm (>>40 in) in men or 40 in) in men or >>88 cm (88 cm (>>35 in) in women35 in) in womenexcept in Germany (>103 cm [41 in] and >92 cm [36 in], respectivexcept in Germany (>103 cm [41 in] and >92 cm [36 in], respectively)ely)
Abdominal obesity Abdominal obesity has reached epidemic has reached epidemic proportions worldwideproportions worldwide
Swiss Statistical Federal Office 2003 Swiss Statistical Federal Office 2003 Percentage of obesityPercentage of obesity
Obesity Obesity in Switzerlandin Switzerland
Patients with abdominal Patients with abdominal obesity (high waist obesity (high waist circumference) often circumference) often present with one or more present with one or more additional additional CV risk factors CV risk factors
CV risk factors in a typical patient with abdominal obesityCV risk factors in a typical patient with abdominal obesity
High waist circumference is associated with High waist circumference is associated with multiple cardio vascular risk factorsmultiple cardio vascular risk factors
115 cm115 cm
1.7 mmol/l1.7 mmol/l
0.9 mmol/l0.9 mmol/l
6.5 mmol/l6.5 mmol/l
Adverse Adverse cardiometaboliccardiometabolic effects of effects of products of products of adipocytesadipocytes
AdiposeAdiposetissuetissue
↑↑ ILIL--66
↓↓ AdiponectinAdiponectin
↑↑ LeptinLeptin
↑↑ TNFTNFαα
↑↑ AdipsinAdipsin(Complement D)(Complement D)
↑↑ PlasminogenPlasminogenactivator inhibitoractivator inhibitor--11
(PAI(PAI--1)1)
↑↑ ResistinResistin
↑↑ FFAFFA
↑↑ InsulinInsulin
↑↑ AgiotensinogenAgiotensinogen
↑↑ Lipoprotein lipaseLipoprotein lipase
↑↑ LactateLactate
InflammationInflammation
TypeType2 diabetes2 diabetes
HypertensionHypertension
AtherogenicAtherogenicdyslipidaemiadyslipidaemia
ThrombosisThrombosisAtherosclerosisAtherosclerosis
BrBr J J NutrNutr 20042004;92:347;92:347
<71<71 7171––75.975.9 7676––8181 81.181.1––8686 86.186.1––9191 91.191.1––96.396.3 >96.3>96.3
2424
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Waist circumference (cm)Waist circumference (cm)
Am J Am J EpidemiolEpidemiol 19971997;145:614;145:614
Abdominal obesity increases the risk of Abdominal obesity increases the risk of developing type 2 diabetesdeveloping type 2 diabetes
WomenWomen
Intra abdominal adiposity impairs pancreatic Intra abdominal adiposity impairs pancreatic ββ--cell functioncell function
Long-term damageto β-cellsDecreased insulinsecretion
Short-termstimulationof insulinsecretion
Intra abdominal Intra abdominal adiposityadiposity
FFA: Free fatty acidsFFA: Free fatty acids
SplanchnicSplanchnic & systemic& systemiccirculationcirculation
DiabetesDiabetes 19921992;41:826;41:826
310310
248248
186186
124124
6262
00
6060
4545
3030m
g/d
Lm
g/d
L
mg/
dL
mg/
dL
TriglyceridesTriglycerides
LeanLean
HDLHDL--cholesterolcholesterol
Visceral fatVisceral fat(obese subjects)(obese subjects)
LowLow HighHigh LeanLean
Visceral fatVisceral fat(obese subjects)(obese subjects)
LowLow HighHigh
IntraIntra--abdominal adiposity and abdominal adiposity and dyslipidaemiadyslipidaemia
LancetLancet 20042004;364:937;364:937
PA
R (
%)
PA
R (
%)aa
aaProportionProportion of MI in the total population attributable to a specific risk fof MI in the total population attributable to a specific risk factoractor
Abdominal obesity predicts the Abdominal obesity predicts the risk of CVD beyond BMIrisk of CVD beyond BMI
Cardiometabolic risk factors in the Cardiometabolic risk factors in the InterHeartInterHeart StudyStudy
00
2020
4040
6060
1818
HTNHTN
1010
DiabetesDiabetes
2020
AbdominalAbdominalObesityObesity
4949
AbnAbn LipidsLipids
Abdominal obesity: a major underlying Abdominal obesity: a major underlying cause of acute myocardial infarctioncause of acute myocardial infarction
LancetLancet 20020044;;364364::937937
CardiovascularCardiovascular RiskRisk FactorsFactors
Am Am HeartHeart JJ 20052005;149:54;149:54
Ad
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11 11 11
1.171.17 1.161.16 1.141.14
1.291.29 1.271.27
1.351.35
0.80.8
11
1.21.2
1.41.4
CVD deathCVD death MIMI AllAll--cause deathscause deaths
Tertile 1Tertile 1Tertile 2Tertile 2
Tertile 3Tertile 3
MenMen WomenWomen<95<95
9595––103103
>103>103
<87<878787––9898
>98>98
Waist circ. (cm):Waist circ. (cm):
Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDLAdjusted for BMI, age, smoking, sex, CVD disease, DM, HDL--C, totalC, total--CC
The HOPE StudyThe HOPE Study
Abdominal obesity and increased Abdominal obesity and increased risk of cardiovascular eventsrisk of cardiovascular events
•• Abdominal obesity (visceral)Abdominal obesity (visceral)
•• is often associated with other CV risk factorsis often associated with other CV risk factors
•• is an independent CV risk factoris an independent CV risk factor
•• AdipocytesAdipocytes are metabolically active endocrine are metabolically active endocrine organs, not simply inert fat storageorgans, not simply inert fat storage
Why is abdominal obesity harmful ?Why is abdominal obesity harmful ?
IntraIntra--AbdominalAbdominalAdiposityAdiposity
CVCVdiseasedisease
CardiovascularCardiovascularrisk factorsrisk factors
DirectDirect
IndirectIndirect
IntraIntra--abdominal adiposity is abdominal adiposity is characterisedcharacterised by accumulation ofby accumulation offat around and inside abdominal organsfat around and inside abdominal organs
ObesObes ResRes 20032003;11:1278;11:1278
Abdominal obesityAbdominal obesity(High waist circumference)(High waist circumference)
IntraIntra--abdominal adiposity: abdominal adiposity: a a rootroot cause of cause of cardiometaboliccardiometabolic diseasedisease
Le systLe systèème EC est un systme EC est un systèème endogme endogèène et physiologique qui joue un rne et physiologique qui joue un rôle ôle clcléé dans la rdans la réégulation de lgulation de l’’homhomééostasie ostasie éénergnergéétique et de ltique et de l’’accumulation de accumulation de graisse, aussi bien que dans le mgraisse, aussi bien que dans le méétabolisme tabolisme glucogluco--lipidiquelipidique..
LL’’expression des rexpression des réécepteurs CBcepteurs CB11 est trest trèès rs réépandue. On les trouve dans des pandue. On les trouve dans des rréégions du cerveau et dans divers tissus pgions du cerveau et dans divers tissus péériphriphéériques tels que le tissu riques tels que le tissu adipeux, les muscles et le foie.adipeux, les muscles et le foie.
Le blocage du rLe blocage du réécepteur CBcepteur CB11 pourrait devenir une nouvelle approche pour pourrait devenir une nouvelle approche pour rrééduire plusieurs facteurs de risques duire plusieurs facteurs de risques cardiomcardioméétaboliquestaboliques en adressant en adressant ll’’obobéésitsitéé abdominale et en amabdominale et en amééliorant directement le mliorant directement le méétabolisme tabolisme glucogluco--lipidique ainsi que la rlipidique ainsi que la réésistance sistance àà ll’’insuline.insuline.
Le Le SystSystèèmeme EndocannabinoEndocannabinoïïdede
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Remodelage des phospholipidesRemodelage des phospholipides
PrPréécurseurs dcurseurs déérivrivééssphospholipidiquesphospholipidiques
EndocannabinoEndocannabinoïïdesdes
Produits de dProduits de déégradationgradation
•• Sont Sont immimméédiatement mdiatement méétabolistabolisééss apraprèès leur actions leur action•• Agissent localementAgissent localement
OO
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ll’’Acide GrasAcide Gras
Les Les EndocannabinoEndocannabinoïïdesdes sont produits sur sont produits sur demande par la demande par la mmembraneembrane ccellulaireellulaire
ModModèèles pour les pour éétudier le systtudier le systèème ECme EC
(A) (A) BlocageBlocage PharmacologiquePharmacologique des des rréécepteurscepteursCBCB11 chezchez la la sourissouris et le ratet le rat
AntagonistesAntagonistes du du rréécepteurcepteur CBCB11
e.ge.g.: Rimonabant.: Rimonabant
•• PhPhéénotype comportementalnotype comportemental•• Analyse molAnalyse molééculaire des tissusculaire des tissus
(B) (B) DDééletionletion ggéénnéétiquetique du du rréécepteurcepteur CBCB11 chezchez la la sourissouris
HNHN
NN
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ClCl
OO
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LL’’Anandamide injectAnandamide injectéée dans le dans l’’hypothalamus induit une hyperphagie chez des hypothalamus induit une hyperphagie chez des rats rassasirats rassasiéés au prs au prééalable. Le Rimonabant attenue cet effet.alable. Le Rimonabant attenue cet effet.
LL’’activation des ractivation des réécepteurs CBcepteurs CB11 par les par les EndocannabinoEndocannabinoïïdes stimule la prise alimentairedes stimule la prise alimentaire
BrBr J PharmacolJ Pharmacol 20012001;134:1151;134:1151
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----
----
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La souris CBLa souris CB11--//-- montre une rmontre une rééduction du poids duction du poids corporel et de la masse grassecorporel et de la masse grasse
CBCB11+/++/+
CBCB11--//--
Age (semaine)Age (semaine)22 44 66 88 1010 1212 1414 1616
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J Clin InvestJ Clin Invest 20032003;112:423;112:423
Mol PharmacolMol Pharmacol 2003;63:908 2003;63:908
CBCB11 est rest réégulguléé àà la hausse dans les adipocytes des rats la hausse dans les adipocytes des rats Fa/fa et dans les adipocytes normaux diffFa/fa et dans les adipocytes normaux difféérencirenciééss
RRéécepteurcepteur
Upregulation de lUpregulation de l’’ARNm du rARNm du réécepteur CBcepteur CB11
•• Dans le TAB du rat obDans le TAB du rat obèèse se ZuckerZucker--fa/fafa/fa
•• Dans les adipocytes 3T3 F442A de sourisDans les adipocytes 3T3 F442A de souris
Cellules 3T3 F442ACellules 3T3 F442A
ND DND D
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WT WT fa/fafa/fa
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Le blocage de CBLe blocage de CB11 par le Rimonabant stimule la par le Rimonabant stimule la production dproduction d’’adiponectine dans les adipocytesadiponectine dans les adipocytes
Rimonabant (Rimonabant (nMnM))
Rimonabant (Rimonabant (nMnM))
Niveau de Niveau de protprotééinesines
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Mol PharmacolMol Pharmacol 2003;63:908 2003;63:908
RimonabantRimonabant –– + + ++(10 mg/kg/d)(10 mg/kg/d)
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Rats obRats obèèse (fa/fa)se (fa/fa)Rats maigresRats maigres
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–– + + ++
Souris CBSouris CB1 1 +/++/+Souris CBSouris CB11 –– //––
**
Effet du Rimonabant sur les niveaux de ARNm dEffet du Rimonabant sur les niveaux de ARNm d’’aadiponectinediponectinechez les rats maigres et obchez les rats maigres et obèèses et le souris CBses et le souris CB11--//--
*P<0.05; **P<0.01 vs V*P<0.05; **P<0.01 vs Vééhiculehicule
LL’’adiponectineadiponectine: : uneune protprotééineine sséécrcrééttééeespspéécifiquementcifiquement par les par les tissustissus adipeuxadipeux
Propriétés anti-athérogéniques:↓ Expression de molécules d’adhésion↓ Adhésion des monocytes aux cellules endothéliales↓ Captage du LDL oxydé↓ Formation de cellules spumeuses↓ Prolifération et migration des cellules musculaires lisses
PropriPropriééttéés antis anti--athathéérogrogééniquesniques::↓↓ Expression de molExpression de moléécules dcules d’’adhadhéésionsion↓↓ AdhAdhéésion des monocytes aux cellules endothsion des monocytes aux cellules endothéélialesliales↓↓ Captage du LDL oxydCaptage du LDL oxydéé↓↓ Formation de cellules spumeusesFormation de cellules spumeuses↓↓ ProlifProliféération et migration des cellules musculaires lissesration et migration des cellules musculaires lisses
Propriétés anti-diabétiques :↑ Sensibilité à l’insuline↑ Captage musculaire de glucose et oxydation des AGL↓ Production hépatique de glucose↓ Triglycérides intracellulaires
PropriPropriééttéés antis anti--diabdiabéétiques :tiques :↑↑ SensibilitSensibilitéé àà ll’’insulineinsuline↑↑ Captage musculaire de glucose et oxydation des AGLCaptage musculaire de glucose et oxydation des AGL↓↓ Production hProduction héépatique de glucosepatique de glucose↓↓ TriglycTriglycéérides intracellulairesrides intracellulaires
0 0 --
2 2 --
4 4 --
6 6 --
8 8 --
10 10 --
12 12 --
14 14 --A
dip
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tin
Ad
ipon
ecti
nle
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leve
ls(( u
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mL
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mL
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LeanLeanIAA (obese subjects)IAA (obese subjects)
LowLow HighHigh
IAA IAA isis associatedassociated withwith reducedreduced adiponectinadiponectin levelslevels
J Clin J Clin EndocrinolEndocrinol MetabMetab 20052005;90:1434;90:1434
JAMAJAMA 20042004;291:1730;291:1730
Rel
ativ
e ri
sk (
95%
CI)
Rel
ativ
e ri
sk (
95%
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Risk of MI for highest Risk of MI for highest vsvs. lowest quintile of adiponectin. lowest quintile of adiponectin
Adj. forAdj. for age;age;date of blooddate of blood
draw; smokingdraw; smoking
+ Adj. for family+ Adj. for familyhistory; alcohol;history; alcohol;
exerciseexercise
+ Adj. for HbA+ Adj. for HbA1C1C;;CRP; HDLCRP; HDL--C;C;
LDLLDL--CC
p<0.001p<0.001p<0.001p<0.001
p=0.02p=0.02
0,00,0
0,20,2
0,40,4
0,60,6
0,80,8
1,01,0
Relationship between Relationship between adiponectinadiponectinlevels and risk of MIlevels and risk of MI
Localisations des rLocalisations des réécepteurs CBcepteurs CB11 et effets du et effets du blocage des rblocage des réécepteurs CBcepteurs CB11
Sites dSites d’’actionaction MMéécanisme(s)canisme(s) ImplicationsImplications
Hypothalamus / Hypothalamus /
Noyau Noyau accumbensaccumbensPrise alimentairePrise alimentaire PoidsPoids
AdipositAdipositéé intra abdominaleintra abdominale
Tissus adipeuxTissus adipeuxAdiponectineAdiponectineLLipogenipogenèèsese
DyslipidDyslipidéémiemie
RRéésistance sistance àà ll’’insuline insuline
MusclesMusclesCaptation duCaptation du
glucoseglucoseRRéésistance sistance àà ll’’insulineinsuline
FoieFoieLLipogenipogenèèsese DyslipidDyslipidéémiemie
RRéésistance sistance àà ll’’insulineinsuline
Tractus GITractus GISignaux de Signaux de
satisatiééttéé
PoidsPoids
AdipositAdipositéé intraintra--abdominaleabdominale
IntraIntra--abdominal adiposity and cardiovascular riskabdominal adiposity and cardiovascular risk
BMJBMJ 20052005;322:716;322:716
LancetLancet 20052005;365:1389;365:1389
Treatment of IntraTreatment of Intra--abdominal adiposityabdominal adiposity
Treatment of IntraTreatment of Intra--abdominal adiposityabdominal adiposity
LancetLancet 20052005;365:1389;365:1389
Treatment of IntraTreatment of Intra--abdominal adiposityabdominal adiposity
LancetLancet 20052005;365:1389;365:1389
Endocannabinoid and cardiovascular riskEndocannabinoid and cardiovascular risk
N Engl J MedN Engl J Med NovemberNovember 17, 17, 20052005;353:2121;353:2121
IntraIntra--abdominal adiposity and cardiovascular riskabdominal adiposity and cardiovascular risk
BMJBMJ 20052005;322:716;322:716
IntraIntra--abdominal adiposity and cardiovascular riskabdominal adiposity and cardiovascular risk
LancetLancet 20052005;365:1389;365:1389
Multiple Multiple secretorysecretoryproductsproductsLiverLiverPancreasPancreas
MuscleMuscle
VasculatureVasculature
Current View: Current View: secretory secretory/endocrine organ /endocrine organOld View: inert storage depot Old View: inert storage depot
Fatty acids GlucoseFatty acids Glucose
Fatty acids GlycerolF
atty acids G
lycerol
Fed Fed
Fasted Fasted
TgTg
TgTg
TgTg
The evolving view of adipose tissue:The evolving view of adipose tissue:an endocrine organ an endocrine organ
Le Le blocageblocage de CB1 de CB1 rrééduitduit de multiples de multiples facteursfacteurs de de risquerisque caridomcaridoméétaboliquestaboliques
SyndrSyndrome ome MMéétaboliquetabolique
Obésité abdominale(HWC)*
Blocage de CB1
AdipositéIntra-abdominale
Mode inflammatoireMode inflammatoire
DyslipidémieAthérogénique• Faible HDL-C • TG élevés• Petites, denses particules de LDL
Intolérance au glucoseRésistance à l’insuline• Hyperinsulinémie• Diabètes de type 2
*HWC = High waist circumference*HWC = High waist circumference
Dr. FranDr. Franççois Mach, MDois Mach, MDDivision de Division de CardiologieCardiologie
DDéépartementpartement de de MMéédecinedecine InterneInterneHôpital Universitaire de GenHôpital Universitaire de Genèèveve
[email protected]@medecine.unige.ch
www.cardiologywww.cardiology--geneva.chgeneva.ch
HUG, GenHUG, Genèève, le 2 mars 2006ve, le 2 mars 2006
MerciMerci
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