Women @ Heart The link between visceral fat and Athersclerosis

1. Women @ HeartThe link between visceral fat and Athersclerosis By Ashraf Reda MD Prof and Head of Cardiology Dep Menofia university

2. If they have menopause men may have andropause

3. Describe the pathophysiology of intra-abdominal adiposity. • Define the role of intra-abdominal adiposity as a major cause of cardiometabolic disease. • Discuss current research related to CB1 blockade as a novel approach to cardiometabolic disease management.

5. Intra-abdominal adipose tissue Lipolysis Abdominal obesity PV FFAs Cluster of metabolic & CV RFs Liver Metabolic syndrome Hepatic ins.R. Small LDL particles HDL

6. VLDL FFAc Liver (Fatty liver) Glucose B-cells Insulin Sk. Msc ( Ectopic fat) Hyperinulinemia (Insulin Resistence)

7. Effect of plasma FFA Adipose tissue FFA TG Liver FFA HL TG HDL3 HDL2 CETP CE HL CE VLDL CETP TG LDL LDL

8. Dyslipidemia not hyperlipidemia • We have to think both quantitavely and qualitatively • Looking at total cholesterol or LDL level is not enough

9. Lipid profile among patients with ACS incardiology dep. Menofia university No % Mean (mg/dl) TC < 200mg/dl 25/40 62.5 160.3 Mean BNP 943.2 (N: up to 350) TC > 200mg/dl 15/40 37.5 238.9 Mean BNP 1376 TGs < 200 32/40 80 137.2 Mean BNP 988 TGs > 200 8/40 20 254 Mean BNP 1599.7 Data from file: Reda et al 2003

10. Abdominal obesity and not BMI Body fat distribution not body weight

11. CB1 Lipoprotein lipase activity Adipose tissue --- TNF-a Adiponectin Fat accumulation in adipose T --- Adeponectin ---- + + ---- FA oxidation Glucose uptake FFA clearance Insulin sensetivity Muscle

12. Blocking CB1 receptors can decrease intraabdominal obesity • Oral cannabinoid therapy reduces progression of atherosclerosis Activation of CB2 receptor may stop atherosclerosis progression eg: TetraHydroCannabinol (THC) by stimulating CB2 in mice but Smoking marijuana still bad for you!

13. Blocking the over-activated endocannbinoid system CB1 blockade Central CB1 Blockade Perepheral CB1 blockade (Adipose tissue) Food intake Eess abdominal fat Adeponectin Insulin Resistence Alter the atherogenic lipid profile CRP

14. Changes in weight and waist size in the rimonabant- and placebo-treated groups Scheen A. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA.

15. HDL cholesterol and triglyceride parameters in the rimonabant- and placebo-treated groups Scheen A. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA.

16. Visceral, subcutaneous fat linked to metabolic syndrome, even in normal-weight individualsApr 11, 2005 Shelley Wood • The association between higher visceral fat and metabolic syndrome was particularly noticeable in normal-weight and overweight men and women, but less so in the obese. • Higher subcutaneous adipose tissue as well as higher intermuscular adipose tissue was significantly associated with metabolic syndrome in normal-weight and overweight, but not in obese, men, and not in women.

17. CONCLUSIONS • Describe the pathophysiology of intra-abdominal adiposity. • Define the role of intra-abdominal adiposity as a major cause of cardiometabolic disease. • Discuss current research related to CB1 blockade as a novel approach to cardiometabolic disease management.