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- May 11, 2008 |
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| Presentation |
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"Adiponectin and the metabolic syndrome"Dr. Tohru Funahashi (biography)
English - 2003-03-29 - 56 minutes
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Summary :
The metabolic syndrome, which clusters insulin resistance, hypertension and dyslipidemia, is a common basis of type 2 diabetes and atherosclerotic vascular diseases. Although the molecular link between visceral fat and the metabolic syndrome remains unclear, accumulation of intra-abdominal visceral fat is a major risk of the metabolic syndrome. We discovered a novel adipocyte-specific factor, adiponectin, through a human adipose tissues cDNA project. Adiponectin circulates in human plasma with a concentration of 5-10 mcg/mL, but its levels are decreased in subjects with visceral obesity. Adiponectin exhibits pleiotropic effects on vascular cells, modifying endothelial cell function, proliferation of smooth muscle cells and lipid accumulation of macrophages. Furthermore, adiponectin augments glucose uptake of myocytes. Adiponectin-null mice exhibit severe diet-induced insulin resistance and neointimal thickening in response to vascular injury. Overexpression of adiponectin in apoE knockout mice reduces fatty streak formation in aorta. Recently, an NIH group showed adiponectin was a protective marker for the development of type 2 diabetes in Pima Indians, and a group in Italy reported that high plasma adiponectin was a negative risk for cardiovascular events in renal insufficiency. Adiponectin, a self-defence molecule produced by adipocyte, will be a new therapeutic target against the metabolic syndrome.
Learning objectives :
The participant will be introduced to adiponectin, a novel adipocyte-specific factor which will represent a new therapeutic target against the metabolic syndrome.
Bibliographic references :
Diabetes 2003 Apr;52(4):910-917
Human Metabolic Syndrome Resulting From Dominant-Negative Mutations in the Nuclear Receptor Peroxisome Proliferator-Activated Receptor-gamma.
Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M, Williams RL, Umpleby AM, Thomas EL, Bell JD, Dixon AK, Dunne F, Boiani R, Cinti S, Vidal-Puig A, Karpe F, Chatterjee VK, O'Rahilly S.
Diabetes 2002 Jul;51(7):2325-8
Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.
Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kawamoto T, Sumitsuji S, Funahashi T, Matsuzawa Y.
Diabetes Care 2002 Feb;25(2):376-80
Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients.
Yang WS, Jeng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM.
J Clin Endocrinol Metab 2001 Sep;86(9):4321
The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome.
Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AE, Maas D, Takahashi M, Kihara S, Tanaka S, Matsuzawa Y, Blangero J, Cohen D, Kissebah A.
Nat Med 2001 Aug;7(8):941-6
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T.
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