Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy

Ilchiro Shimomura, Robert E Hammer, Shinji Ikemoto, Michael S Brown, Joseph L Goldstein

Research output: Contribution to journalArticle

788 Citations (Scopus)

Abstract

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver. We have developed a mouse model that mimics these features of CGL: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.

Original languageEnglish (US)
Pages (from-to)73-76
Number of pages4
JournalNature
Volume401
Issue number6748
DOIs
StatePublished - Sep 2 1999

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Lipodystrophy
Congenital Generalized Lipodystrophy
Leptin
Insulin Resistance
Diabetes Mellitus
Fats
Adipose Tissue
Eating
Sterol Regulatory Element Binding Protein 1
Hepatomegaly
Hyperinsulinism
Fatty Liver
Nuclear Proteins
Hyperglycemia
Energy Metabolism
Transgenic Mice
Parturition
Hormones
Glucose
Food

ASJC Scopus subject areas

  • General

Cite this

Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. / Shimomura, Ilchiro; Hammer, Robert E; Ikemoto, Shinji; Brown, Michael S; Goldstein, Joseph L.

In: Nature, Vol. 401, No. 6748, 02.09.1999, p. 73-76.

Research output: Contribution to journalArticle

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