A transgenic model of visceral obesity and the metabolic syndrome

H Masuzaki; J Paterson; H Shinyama; N M Morton; J J Mullins; J R Seckl; J S Flier

doi:10.1126/science.1066285

A transgenic model of visceral obesity and the metabolic syndrome

Science. 2001 Dec 7;294(5549):2166-70. doi: 10.1126/science.1066285.

Authors

H Masuzaki¹, J Paterson, H Shinyama, N M Morton, J J Mullins, J R Seckl, J S Flier

Affiliation

¹ Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.

PMID: 11739957
DOI: 10.1126/science.1066285

Abstract

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

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1
Abdomen
Adipocytes / cytology
Adipocytes / pathology
Adipose Tissue / enzymology*
Adipose Tissue / metabolism
Animals
Body Composition
Cell Size
Corticosterone / blood
Corticosterone / metabolism
Dietary Fats / administration & dosage
Disease Models, Animal*
Eating
Gene Targeting
Humans
Hydroxysteroid Dehydrogenases / genetics
Hydroxysteroid Dehydrogenases / metabolism*
Hyperglycemia / metabolism
Hyperinsulinism / metabolism
Insulin Resistance
Leptin / metabolism
Lipid Metabolism
Lipids / blood
Lipoprotein Lipase / genetics
Lipoprotein Lipase / metabolism
Male
Metabolic Syndrome*
Mice
Mice, Transgenic
Obesity / enzymology*
Obesity / genetics*
Receptors, Glucocorticoid / genetics
Receptors, Glucocorticoid / metabolism
Viscera
Weight Gain

Substances

Dietary Fats
Leptin
Lipids
Receptors, Glucocorticoid
glucocorticoid receptor alpha
Hydroxysteroid Dehydrogenases
11-beta-Hydroxysteroid Dehydrogenase Type 1
HSD11B1 protein, human
Lipoprotein Lipase
Corticosterone