acides gras oméga-3 et santé

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Acides Gras Oméga-3 et Santé Yvon A. Carpentier Laboratoire de Chirurgie Expérimentale ULB Clinique des Lipides Hôpital Erasme

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Acides Gras Oméga-3 et Santé. Yvon A. Carpentier Laboratoire de Chirurgie Expérimentale ULB Clinique des Lipides Hôpital Erasme. Structure et nomenclature des acides gras. H 3 C. COOH. 18:0. Acide stéarique. 9. H 3 C. COOH. 18:1n-9. Acide oléique. H 3 C. COOH. 18:2n-6. - PowerPoint PPT Presentation

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Page 1: Acides Gras Oméga-3 et Santé

Acides Gras Oméga-3 et Santé

Yvon A. Carpentier

• Laboratoire de Chirurgie Expérimentale ULB

• Clinique des Lipides

Hôpital Erasme

Page 2: Acides Gras Oméga-3 et Santé

Structure etStructure et nomenclature des acides gras nomenclature des acides gras

COOH

H3C

H3C COOH

H3C

COOH

Acide stéarique 18:0

Acide oléique 18:1n-9

Acide linoléique 18:2n-6

Acide-linolénique 18:3n-3H3C COOH

9

6

3

Page 3: Acides Gras Oméga-3 et Santé

Solide à température ambiante vs. Liquide à température ambianteSolide à température ambiante vs. Liquide à température ambiante

Page 4: Acides Gras Oméga-3 et Santé

n-6 serie n-3 serie

Linoleic ac. Alpha-linolenic ac.

C18:2n-6 C18:3n-3

6-desaturase

Gamma-linolenic ac. Octadecatetraenoïc ac.

C18:3n-6 C18:4n-3

Elongation

Dihomo-gamma-linolenic ac. Eicosatetraenoïc ac.

C20:3n-6 C20:4n-3

5-desaturase

Arachidonic ac. Eicosapentaenoïc ac.

C20:4n-6 C20:5n-3

Elongation

Docosatetraenoïc ac. Docosapentaenoïc ac.

C22:4n-6 C24:5n-6 C24:6n-3 C22:5n-3

Docosapentaenoïc ac. Docosahexaenoïc ac.

C22:5n-6 C22:6n-3

EPA

DPA

DHA

AA

Elongation - unsaturation of essential FA

Page 5: Acides Gras Oméga-3 et Santé

Metabolism of -linolenic acid

From Cunnane SC, J Physiol Pharmacol, 1996

Page 6: Acides Gras Oméga-3 et Santé

Trends in the intake of fatty acids in the UKTrends in the intake of fatty acids in the UK

% Energy% Energy

5050

4040

3030

2020

1010

0019401940 1950 1950 1960 1960 1970 1970 1980 1980 1990 1990

PUFA to SFA ratio

1

0.8

0.6

0.4

0.2

0

Total fatTotal fat

SFASFAMUFAMUFA

PUFAPUFA

Page 7: Acides Gras Oméga-3 et Santé

Last 30 Years - Large Increase in the Intake of n-6 PUFAs in Industrialized Countries

Last 30 Years - Large Increase in the Intake of n-6 PUFAs in Industrialized Countries

•Between 1972 and 1998 the n-6 fatty acids rose from 4% to 6%.

•Upsurge of Asthma in the UK, Australia, New Zealand and Germany might be a related phenomenon.

•The unexplained increase in the incidence of edema, allergic rhinitis, and regional differences of inflammatory diseases within countries may relate to increased n-6 fatty acid intake.

Roberts 1991, Dept. of Health UK 1994,Black and Sharp 1997, Lewis et al. 1996, Grimble 1998

Fü-Out-13b

Page 8: Acides Gras Oméga-3 et Santé

Evolution des habitudes alimentaires

Paléolithique « Western » AHA

• Lipides (% cal) 21 34 <30

• Sat (% cal) <10 ~13 <10

• P:S 1.4 ~0.5 >1.0-3/ -6 1/1-1/2 1/10-1/20 1/1-1/5

• Fibres (g/j) ~46 ~20 >25

Page 9: Acides Gras Oméga-3 et Santé

DONNEES EPIDEMIOLOGIQUES

Populations consommant bcp AG n-3

• faible incidence de pathologies cardiovasculaires• faible incidence de pathologies inflammatoires et allergiques• faible incidence de cancers (colon, sein, prostate)• faible incidence de lithiases rénales• faible incidence de diabète type I• allongement de durée de gestation• incidence accrue d’insuffisance rénale chronique

CORRELATION AVEC COMPOSITION EN ACIDES GRAS DES

MEMBRANES CELLULAIRES ET FORMATION EICOSANOIDES

Page 10: Acides Gras Oméga-3 et Santé

Acides Gras oméga-3Rôles-clés en Santé Humaine

• Développement cognitif• Développement vision• Réponses immunes/inflammatoires• Grossesses & développement foetal• Maladies neurodégénératives • Aspects psychologiques• Maladies cardio-vasculaires

Page 11: Acides Gras Oméga-3 et Santé
Page 12: Acides Gras Oméga-3 et Santé

Modes and sites of action of n-3 PUFA’s

• Formation of eicosanoids

(tissue level, locally and at distance)

Page 13: Acides Gras Oméga-3 et Santé

Membrane Pool (PL)

F2-isoprostanes

Metabolic Pool (TG, FFA)

18:2 n-6 18:3 n-6 20:3 n-6 20:4 n-6 (LA) (GLA) (DGLA) (AA)

Cyclo -oxygenase

PGI2 PGE2TXA2

PGE1

Lipoxygénases

LT4 HETES

Page 14: Acides Gras Oméga-3 et Santé

Arachidonic acid in cell membrane phospholipidArachidonic acid in cell membrane phospholipid

Free arachidonic acidFree arachidonic acid

Phospholipase APhospholipase A22

PGGPGG22

PGHPGH22

15-HPETE15-HPETE 12-HPETE12-HPETE 5-HPETE5-HPETE

15-HETE15-HETE 12-HETE12-HETE LTALTA44 5-HETE5-HETE

PGDPGD22

PGEPGE22

PGIPGI22 TXATXA22

PGFPGF22

LXALXA44 LTCLTC44 LTBLTB44

LTDLTD44 LTELTE44

A major role of arachidonic acid is as A major role of arachidonic acid is as a precursor for eicosanoidsa precursor for eicosanoids

COX 15-LOX 12-LOX 5-LOX

Page 15: Acides Gras Oméga-3 et Santé

Membrane Pool (PL)

F3 - and F4 - isoprostanes

Metabolic Pool (TG, FFA)

18:3 n-3 20:5 n-3 22:5 n-3 22:6 n-3 (ALA) (EPA) (DGLA) (DHA)

Cyclo-oxygénases

PGI3 PGE3

TXA3

Lipoxygenases

LT5

Page 16: Acides Gras Oméga-3 et Santé

Eicosanoids derived from n-3 (vs. n-6) PUFAs

• Less inflammatory

• Less thrombogenic

• Less chemo-attractive

• Weaker protection of gastro-intestinal mucosa

• Retard delivery (increase pregnancy duration)

Page 17: Acides Gras Oméga-3 et Santé

Arachidonic acid in membrane phospholipids

Free arachidonic acid

2-series PG and TX 4-series LT

COX-2

5-LOX

Phospholipase A2

Inflammatory effects Inflammatory effects

EPADHA

Classic view of the anti-inflammatory Classic view of the anti-inflammatory action of long chain action of long chain -3 PUFA-3 PUFA

Page 18: Acides Gras Oméga-3 et Santé

Resolvins & related compoundsResolvins & related compounds

EPAEPA DHADHA

E-series resolvinsE-series resolvins D-series resolvins, D-series resolvins, neuroprotectins etc.neuroprotectins etc.

Anti-inflammatory; inflammation resolvingAnti-inflammatory; inflammation resolving

COX-2 (& presence of aspirin)COX-2 (& presence of aspirin)

Page 19: Acides Gras Oméga-3 et Santé
Page 20: Acides Gras Oméga-3 et Santé

From J.A. Ross et al, Curr Opin Clin Nutr Metab Care, 1999

Possible sites of action of n-3 & n-6 PUFAs

Page 21: Acides Gras Oméga-3 et Santé

Modes and sites of action of n-3 PUFA’s

• Formation of eicosanoids

(tissue level, locally and at distance)

• Components of membrane phospholipids

(membrane physical properties & interaction with membrane proteins : cell level)

• Second messengers in signalling pathways (molecular level)

• Regulators of gene expression (transcription factors : molecular level)

Page 22: Acides Gras Oméga-3 et Santé

Signalisation cellulaire: voie des MAP-Kinases

Page 23: Acides Gras Oméga-3 et Santé

AdhesionAdhesion

ChemoattractantsChemoattractants

EicosanoidsEicosanoids

CytokinesCytokines

Reactive Reactive speciesspecies

PAFPAF

InflammationInflammation

ChemotaxisChemotaxis

InjuryInjury

Page 24: Acides Gras Oméga-3 et Santé

Lipides plasmatiquesPression artérielle

Tendance aux thrombosesRésistance à insuline

OxydationHomocystéineInflammation

Fonction endothélialeIrritabilité ventriculaire

NUTRITION MCV

Nutrition et Pathologies Cardio-vasculaires

From WC Willett, 2004

Page 25: Acides Gras Oméga-3 et Santé

Acides Gras Oméga 3 et le Coeur triglycérides (4g/j) arythmies arrêts cardiaques réactions inflammatoires coagulation• Synergie avec l’aspirine• Pas d’effets secondaires• Pas d’effet sur le cholestérol

morbidité et mortalité des maladies coronaires

Page 26: Acides Gras Oméga-3 et Santé

The New EnglandJournal of Medicine

• Volume 312 May 9, 1985 Number 19

THE INVERSE RELATION BETWEEN FISH CONSUMPTION AND 20-

YEAR MORTALITY FROM CORONARY HEART DISEASE

Daan KROMHOUT, PH.D., M.P.H., EDWARD B., BOSSCHIETER, M.D.,

AND COR DE LEZENNE COULANER, M.SC.

1960: town of Zutphen, the Netherlands

852 middle-aged men without CHD

dietary history

20 year follow-up:

78 deaths from CHD

(> 50%) mortality from CHD in subjects eating > 30 g fish/day

Page 27: Acides Gras Oméga-3 et Santé

2033 men having recovered from myocardial infarction (M.I.)

Dietary intervention in secondary prevention of M.I.

I. fat intake (to 30% energy intake) and P/S ratio (to 1.0)

II. fatty fish intake (200-400g/week)

III. cereal fibre intake (18g/day)

2 year follow-up :

29% REDUCTION OF MORTALITY (all causes) IN ‘‘FISH’’ GROUP II

Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction : diet and reinfarction trial (DART)

M.L. Burr et al., The Lancet, 1989

Page 28: Acides Gras Oméga-3 et Santé

Dietary intake and cell membrane levels of long-chain n-3 Polyunsaturated Fatty Acids and the risk of

primary cardiac arrest

D.C. Siscovick et al.

« Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (... equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [Cl], 0.4 to 0.8), after adjustment for potential confounding factors. »

JAMA, 1995

Page 29: Acides Gras Oméga-3 et Santé

Prevention and termination of arrhythmia by EPA

J.X. Kang & A. Leaf, Proc Natl Acad Sci USA, 1994

Page 30: Acides Gras Oméga-3 et Santé

Dog model of cardiac sudden death

surgically, large myocardial infarct + inflatable cuff around left circumflex coronary art. (LCA)

1 month later:

Treadmill running + LCA occlusion

Ventricular fibrillation and death in all controls & soybean oil (n = 7)

Survival in 5/7 dogs infused for 1h with EPA

6/8 dogs infused for 1h with DHA

6/8 dogs infused for 1h with LNA

Prevention of Sudden Cardiac Death by Dietary Pure -3 Polyunsaturated Fatty Acids in Dogs

G.E. Billman et al, Circulation, 1999

Page 31: Acides Gras Oméga-3 et Santé

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques :

a randomised controlled trial• 188 patients en attente endartériectomie carotide (7-189j)• Suppl. HP (1.4g EPA/DHA/j) vs. Tournesol vs. Palme/Soja

Résultats - Suppl. HP vs. 2 autres groupes: EPA & DHA dans lipides de plaque ( incorporation avec temps)

• Plus de plaques avec couche fibreuse épaisse

• Moins de plaques avec couche fibreuse fine & inflammatoire

• Moins d’infiltration de macrophages dans plaques

t/o rapide des acides gras dans lipides des plaques

effet marqué de suppl. HP sur morphologie & fragilité des plaques F. Thies et al, The Lancet, 2003

Page 32: Acides Gras Oméga-3 et Santé

Dietary Fish Oil Supplementation Reduces Myocardial Infarct Size in a Canine Model

of Ischemia and Reperfusion

0.06 g/kg.day EPA for 6 weeks

Occlusion of left circumflex coronary art. for 90 min followed by 6h

of reperfusion

Infarct size: 13.3% ( 3) vs 29.7% (control) (p<0.05);

no difference in regional blood flow or oxygen consumption

Protective mechanisms:• inhibition of TXA2• inhibition of free radical production by leucocytes?

H. J. Oskarsson et al., J Am Coll Cardiol, 1993

Page 33: Acides Gras Oméga-3 et Santé

Acides Gras -3 et Endothélium

• Amélioration profil lipoprotéines

• Amélioration profil éicosanoïdes

• Effet sur membranes cellulaires (et Chol dans cavéoles)

• Modulation de facteurs de transcription nucléaire

• Amélioration défenses anti-oxidantes de cellule vasorelaxation coagulation, act plaquettes & molécules adhésion sensibilité aux cytokines & radicaux libres activation CML

Page 34: Acides Gras Oméga-3 et Santé

essential for maturation of foetal CNS and retina (DHA)

reduce inflammatory response

anti-thrombotic effect

prevent impaired cellular immunity when caused

by PGE2 production

decrease plasma triglyceride concentration (also post-prandial)

decrease plasma free fatty acid concentration (also p-prandial)

BENEFICIAL EFFECTS OF n-3 PUFA ( I )

Page 35: Acides Gras Oméga-3 et Santé

decrease cell reactivity to various stimuli (e.g. ventricular arrhythmia’s,...)

prevent / reverse cancer & inflammatory cachexia

increase tolerance to organ transplantation and improve function of the graft

help maintaining adequate tissue microperfusion

reduce cellular accumulation of fat (e.g., liver)

potential interest for supplying n-3 PUFA to « acute » patients

BENEFICIAL EFFECTS OF n-3 PUFA ( II )

Page 36: Acides Gras Oméga-3 et Santé

Limitations to n-3 FA supply with Fish Oils

• Gastro-intestinal administration

FO TG : poor substrate for pancreatic lipase

slow & rather unefficient absorption

• Intravenous infusion

FO TG : poor substrate for lipoprotein lipase

slow plasma elimination

! a proportion of n-3 FA used for oxidative purposes !

Page 37: Acides Gras Oméga-3 et Santé
Page 38: Acides Gras Oméga-3 et Santé

Obésité, syndrome métabolique, et insulino-résistance

• Influence du patrimoine génétique• 85% des diabétiques T2 sont obèses• 30% des obèses sont diabétiques (T2) prévalence• Différences entre ethnies (NB: asiatiques)• Influence facteurs comportementaux

(nutrition, activité physique, …)• Relation avec stress & inflammation

Page 39: Acides Gras Oméga-3 et Santé

Le Syndrome Métabolique

• Combinaison de 3 facteurs: - obésité abdominale : tour taille > 94 cm (H) ou > 80 cm (F) - conc. triglycérides 1.7 mmol/L (150 mg/dL) ou traitt - conc. HDL-cholestérol < 1.03 mmol/L (40 mg/dL) H ou traitt < 1.28 mmol/L (50 mg/dL) F ou traitt - tension artérielle 130/85 mm Hg ou traitt - conc. glucose à jeun 5.56 mmol/L (100 mg/dL) ou traitt prévalence: 44% pour population USA > 50 ans (2003) prévalence coronaropathies (>> facteurs isolés)

Page 40: Acides Gras Oméga-3 et Santé

FACTEURS ASSOCIES AU SYNDROME METABOLIQUE

• Insulino-résistance & risque diabète T2

• Dépôts ectopiques de TAG (foie, muscles, … )

• Altérations lipoprotéines (sd LDL athérogènes)

• Composante inflammatoire

• Dysfonction endothéliale

activité ortho-sympathique

Etiologie multiple (nutrition, sédentarité, …)

Page 41: Acides Gras Oméga-3 et Santé

Serum sialic acid concentration in 263 overweight women without (0) or with 1-3 other features of metabolic syndrome : insulin resistance;

dyslipidemia; hypertension

L. Browning, Proc Nut Soc, 2003

Page 42: Acides Gras Oméga-3 et Santé

Gene variants, insulin resistance, and dyslipidaemia

M.Lakso, Curr Opin Lipidol, 2004

Hypotheses: primary effect of variants on insulin resistance or on dyslipidaemia

Page 43: Acides Gras Oméga-3 et Santé

Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in

healthy men

• 8 healthy male volunteers• 60h complete bed rest + high fat or high CHO diet• Hyperinsulinemic –euglycemic clamp (glucose disposal)• 1H-magnetic resonance spectroscopy• Bed rest + high fat : glucose disposal (- 24%) intramyocellular lipid content (+ 32%) R. Stettler et al, Diabetes Care, 2005

Page 44: Acides Gras Oméga-3 et Santé
Page 45: Acides Gras Oméga-3 et Santé

Mitochondrial dysfunction and type 2 diabetes

Maintenance of normal glucose level :• insulin responsiveness of skeletal muscle & liver defect insulin resistance• insulin secretion by pancreatic beta cells defect hyperglycemia

both defects may be caused by mitochondrial dysfunction

Lowell BB & Shulman GI, Science, 2005

Page 46: Acides Gras Oméga-3 et Santé

Insulin resistance associated to obesity and type 2 diabetes

• Molecular defects of insulin signaling in muscle

glucose disposal and transport (role of fatty acids & metabolites)

• Insulin resistance in liver

glucose output (overexpression of glucose-6-Pase)

• Visceral obesity & ectopic fat storage (e.g., muscle & liver)

poor modulation of fat oxidation

• Non-alcoholic fatty liver disease (NAFLD) and steato-hepatitis (NASH) lipolysis, oxidative stress, cytokine induction

• Altered activity of desaturases

9 & 5 6 desaturase DB Savage et al, Hypertension, 2005

Page 47: Acides Gras Oméga-3 et Santé

N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to

type 2 diabetes and obesity ?RAT STUDIES

• N-3 PUFAs improve molecular defects of insulin signaling in muscle

IRS-1 phosphorylation PI 3’-kinase act, GLUT-4 mRNA

muscle TAG content & LCFA CoA

• N-3 PUFAs improve insulin resistance in liver

expression & activity of G-6-Pase; normalize glucose output

• N-3 PUFAs improve visceral obesity & ectopic fat storage (muscle & liver)

fat oxid (PPAR)

lipogenesis, TG formation, & fat deposition

Page 48: Acides Gras Oméga-3 et Santé

N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to

type 2 diabetes and obesity ?HUMAN STUDIES (Healthy volunteers)

• 3 week supplementation w FO (1.1 g EPA + 0.7 g DHA)• Oral glucose load (after supplementation n-3 PUFA) : insulin response (- 40%) glycemic response glucose oxidation lipid oxidation glycogen storage

N.B.: no effect after short-term supplementation (need for n-3 FA incorporation in cell membranes ?)

J. Delarue et al, Reprod Nutr Dev, 2004

Page 49: Acides Gras Oméga-3 et Santé

L. Browning, Proc Nut Soc, 2003

Changes in AUC for insulin (final-baseline) after supplementation with n-3 PUFA vs. placebo in premenopausal non-diabetic subjects

Subjects :

- age : 19-51 years

- BMI : 24-44 kg/m2

P < 0.05

Inflammatory status (IS) :

- low IS : sialic acid < 2.00 mM

- high IS : sialic acid > 2.20 mM

Page 50: Acides Gras Oméga-3 et Santé

Fish oil prevents the adrenal activation elicited by mental stress in healthy men

• 7 healthy volunteers

• 2 tests of mental stress, before & after suppl 7.2g FO/d (3wks)

• Before: heart rate blood pressure energy expenditure

plasma cortisol plasma epinephrine plasma NEFAs

• After n-3 PUFA supplementation :

heart rate blood pressure energy expenditure

plasma cortisol plasma epinephrine plasma NEFAs

blunting of sympatho-adrenal stimulation (at CNS level ?)

potential role in prevention of insulin resistance

J. Delarue et al, Diabetes Metab, 2003

Page 51: Acides Gras Oméga-3 et Santé

Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous

glucose production

• Dietary saturated lipids in healthy subjects:

ins resist but ins secretion glucose tolerance maintained

• Substitution 7% dietary lipids with n-3 PUFA (4 weeks):

reverses peripheral insulin resistance (normal glucose disposal)

HOWEVER:

no suppression of hepatic insulin resistance

no suppression glucose output

no compensatory insulin secretion (+ direct impairment ?)

glucose level MJ Holness et al, Endocrinology, 2003

Page 52: Acides Gras Oméga-3 et Santé

Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics

BMI, serum insulin and/or blood glucose levels: cholesterol synthesis bile acid synthesis cholesterol excretion in bile cholesterol t/o

cholesterol absorption serum cholestanol & plant sterols

PP Simonen et al, Obes Res, 2002

Page 53: Acides Gras Oméga-3 et Santé

FFAFFA FAFA

CHOCHO

TGTG

Apo BApo B

VLDLVLDLapoBapoB

VLDL -TGVLDL -TG

LPLLPL

FAFA

IDLIDL

LDLLDL

Chylo-RChylo-R

ChyloChylo

Visceral Visceral adipose tissueadipose tissue

Lipoprotein metabolism in the metabolic syndrome

Designed from PHR Barett & GF Watts, Curr Opin Lipidol, 2003

LPLLPL

COCO22

Page 54: Acides Gras Oméga-3 et Santé

FFAFFA FAFA

COCO22

TGTG

Apo BApo B

VLDLVLDLapoBapoB

VLDL -TGVLDL -TG

LPLLPL

FAFA

IDLIDL

LDLLDL

Chylo-RChylo-R

ChyloChylo

Visceral Visceral adipose tissueadipose tissue

Designed from PHR Barett & GF Watts, Curr Opin Lipidol, 2003

Lipoprotein metabolism in the metabolic syndrome : Effects of n-3 PUFA supplementation

LPLLPL

CHOCHO

Page 55: Acides Gras Oméga-3 et Santé

N-3 Fatty Acids and Plasma Lipoproteins

plasma triglycerides

plasma VLDL-TG and VLDL-cholesterol

or HDL-cholesterol, but apo A-1

LDL-cholesterol (generally slight)

fraction of small dense LDL (phenotype B subjects)

Page 56: Acides Gras Oméga-3 et Santé

Dietary effects on postprandial triglyceride levels

M. Weintraub et al, J Clin Invest, 1988

SFA

n-6 PUFA

n-3 PUFA

Page 57: Acides Gras Oméga-3 et Santé

Differential effects of n-3 fatty acids

• Mildly hyperlipidemic subjects

- TAG conc. : 1.7g/d EPA+DHA > 9.5g/d ALA

LDL sensitivity to oxidation with 1.7g EPA+DHA

YE Finnegan et al, AJCN, 2003

- TAG conc. : comparable with 4g/d EPA and 4g/d DHA

LDL size : only with 4g/d DHA

forearm blood flow : only with 4g/d DHA

TA Mori et al, AJCN & Circulation, 2000

Page 58: Acides Gras Oméga-3 et Santé

Regulatory effects of HMG CoA reductase inhibitor and Fish Oils on apolipoprotein B-100 kinetics in insulin-resistant obese male

subjects with dyslipidemia

• 48 obese insulin-resistant subjects 6 wks Atorva 40mg vs Omacor 4g vs Atorva+Omacor EPA/DHA : plasma VLDL-apo B

VLDL-apo B secretion VLDL to LDL conversion

Atorva : plasma apo B lipoproteins FCR of VLDL-, IDL-, LDL-apo B

Atorva + EPA/DHA : cumulative effects DC Chan, Diabetes, 2002

Page 59: Acides Gras Oméga-3 et Santé

0

20

40

60

80

100

120

Apo-B (mg/dl)

00,20,40,60,8

11,21,4

Triacylglycerols (mmol/l)

0

1

2

3

4

5

6

Total cholesterol (mmol/l)

00,5

11,5

22,5

33,5

4

LDL-cholesterol (mmol/l)

00,20,40,60,8

11,21,41,6

HDL-cholesterol (mmol/l)

Swedish

Mediterranean

Healthy Swedish Subjects with mild hyperlipidaemia

(after 4 weeks of Mediterranean vs. Swedish diet)

A. Ambring et al, Clin Sci, 2004

P < 0.05P < 0.05

P < 0.05 P < 0.05

Page 60: Acides Gras Oméga-3 et Santé

• Randomized single-blind trial ;120 premenopausal obese women (BMI ≥ 30) with no diabetes, hypertension, or hyperlipidemia

• Low energy mediterranean diet + physical activity vs. Healthy food + exercise

K Esposito et al, JAMA, 2003

Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women

Page 61: Acides Gras Oméga-3 et Santé

Le Syndrome Métabolique: stratégie

• Unique ? AG n-3

effet préventif, non thérapeutique, sur insulino-résistance

inflammation défenses anti-oxydantes cellulaires

(modérée) pression artérielle

TAG HDL-chol sdLDL mais LDL-chol

• Globale nutrition : association avec AG saturés et AGMI

(alimentation type méditerranéen)

amélioration contrôle pondéral

activité physique

si indiquée, association à hypolipémiants

Page 62: Acides Gras Oméga-3 et Santé

Le syndrome métabolique : effets des fibres (FOS) chez le rat

satiété prises alimentaires

absorption glucides & acides gras

glycémie & triglycéridémie post-prandiales

sécrétion insuline

phénomènes inflammatoires (NFkB)

possibilité effets complémentaires et/ou synergiques à ceux des AG w 3

Page 63: Acides Gras Oméga-3 et Santé

Delivery of DHA and EPA via alpha linolenic acid is not efficient

Delivery of DHA and EPA via increased fish oil intake is very

efficient

Current intake of fish oil EPA and DHA in the USA is ~1/3 – 1/6 of

recommended levels

Page 64: Acides Gras Oméga-3 et Santé

General Conclusions and recommendations Fish and Omega-3 fatty acid intake

• Clear benefits in secondary prevention

• Less strong evidence in primary prevention

• Include (fatty) fishes as part of healthy preventive diet

• Temporary limited intake in specific subgroups

(pregnant women & children)

• Increased intake in other specific subgroups

(high risk & hypertriglyceridaemia)

• Possibility to use (good quality) supplements

Page 65: Acides Gras Oméga-3 et Santé

Fish and Omega-3 fatty acid intake :The unanswered questions

• Indications for primary prevention in high risk groups (renal failure, insulin-resistance, transplantation, …) ?

• Doses in different indications ?

• Effect of DHA vs. EPA ?

• Intake of ALA (and w3/w6 intake) ?

• Prevention of lipid peroxidation ?

• Optimising intestinal absorption & cell incorporation ?

Page 66: Acides Gras Oméga-3 et Santé