A Transgenic Model of Visceral Obesity and the Metabolic Syndrome

• DOI: 10.1126/science.1066285
• Publication Date: 2002-07-27T09:47:15Z
• Authors: Hiroaki Masuzaki; Janice Paterson; Hiroshi Shinyama; Nicholas M. Morton; John J. Mullins; Jonathan R. Seckl; Jeffrey S. Flier
• Keywords: Hyperlipidemia

The adverse metabolic consequences of obesity are best predicted by the quantity visceral fat. Excess glucocorticoids produce and diabetes, but circulating glucocorticoid levels normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). We created transgenic mice overexpressing HSD-1 selectively adipose tissue to an extent similar that found obese humans. These had increased corticosterone developed was exaggerated a high-fat diet. also exhibited pronounced insulin-resistant hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte activity may common molecular etiology for syndrome.