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Adiposity in CVD

Adiposity in CVD. Role of adipose tissue in atherogenesis. Overnutrition and genetics. Macrophages. Paracrine and autocrine inflammatory signals. Endocrine inflammatory signals. Fat insulin resistance. Systemic insulin resistance. Muscle insulin resistance. Liver insulin resistance.

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Adiposity in CVD

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  1. Adiposity in CVD

  2. Role of adipose tissue in atherogenesis Overnutrition and genetics Macrophages Paracrine and autocrine inflammatory signals Endocrine inflammatory signals Fatinsulin resistance Systemic insulin resistance Muscle insulin resistance Liver insulin resistance Hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia ATHEROSCLEROSIS Adapted from de Luca C, Olefsky JM. Nat Med. 2006;12:41-2.Lau DCW et al. Am J Physiol Heart Circ Physiol. 2005;288:H2031-41.

  3. Elevated FFA contribute to hypertension, dyslipidemia, and insulin resistance Hypertension C-II C-III HDL-CSmall dense LDL B-100 and Sympathetic nervous system Triglyceride Insulin FFA VLDL Glucose Insulin Glycogen CO2 FFA FFA Triglyceride (intramuscular droplet) VLDL = very low density lipoproteins Eckel RH et al. Lancet. 2005;365:1415-28.

  4. Energy homeostasis is linked to immune balance Optimal nutrition Normal immune function Malnutrition Immunosuppression(susceptibility to infection) Overnutrition Immunoactivation(susceptibility to inflammatory disease) Adapted from Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:1111-9.

  5. Weight gain induces inflammatory changes in adipose tissue Adipocyte Insulin resistance JNKNF-κB TNF-α Leptin Preadipocyte Weight gain VEGF Weight gain Endothelial cell IL-6IL-1βTNF-α Angiogenesis Physical stress/oxidative damage to endothelium? MCP-1 MCP-1 FFA Macrophage recruitment Macrophage recruitment Macrophage Wellen KE, Hotamisligil GS. J Clin Invest. 2003;112:1785-8.

  6. CRP IL-6 PAI-1 Angiotensinogen Leptin Resistin MCP-1 TNF-α Adiponectin Adipose tissue: An endocrine organ Adipocytokines (adipokines) Atherogenic Antiatherogenic Lau DCW et al. Am J Physiol Heart Circ Physiol. 2005;288:H2031-41. Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:1111-9.

  7. Adiponectin associated with decreased risk of MI N = 18,225 men; 6-year follow-up 1.2 1.0 0.8 Relativerisk 0.6 0.4 0.2 0.0 1 2 3 4 5 Adiponectin quintile (95% CI) Plasma level (mg/L) 7.9 12.6 16.5 21.1 29.2 Pischon T et al. JAMA. 2004;291:1730-7.

  8. Endothelial vasodilation Nitric oxide Angiogenesis VCAM-1 TNF- level +proinflammatory effects Insulin sensitivity Oxidized LDL effects on endothelial cells Endothelial cell proliferation/migration Growth factor effects on SMC Neointimal thickening SMC proliferation Beneficial associations of adiponectin Anti-atherogenic features SMC = smooth muscle cells VCAM = vascular cell adhesion molecule Goldstein BJ, Scalia R. J Clin Endocrinol Metab. 2004;89:2563-8. Hopkins TA et al. Cardiovasc Res. 2007.

  9. Low adiponectin in visceral adiposity N = 104 women 30 P < 0.0001 P < 0.01 25 P < 0.0001 Median plasma adiponectin, interquartile range(g/mL) 20 15 10 5 0 Normal weight(n = 20) Lower body adiposity(n = 20) Abdominal adiposity(n = 64) Mean BMI (kg/m2) 25.2 33.4 37.1 Manigrasso MR et al. J Clin Endocrinol Metab. 2005;90:5876-9.

  10. Even moderate weight loss may improve cardiometabolic risk Moderate weight loss ~10% Body weight, which includes ~30% Visceral adipose tissue Blood pressure Lipids Glucose Systolic/Diastolic BP Inflammation Endothelial function Thrombosis susceptibility Total-C LDL -C HDL-C TG non-HDL-C Glycemia Insulin resistance A1C IFG IGT Cardiometabolic risk Manson JE et al. Arch Intern Med. 2004;164:249-58.Després J-P et al. BMJ. 2001;322:716-20.

  11. Summary Adipose tissue is emerging as an important endocrine organ Expansion of visceral adipocytes leads to macrophage infiltration, release of pro-atherogenic adipokines, and decreased secretion of adiponectin Elevated free fatty acid levels act on the liver and skeletal muscle to promote hypertension, dyslipidemia, and insulin resistance

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