Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue

Model for congenital generalized lipodystrophy

Iichiro Shimomura, Robert E Hammer, James A Richardson, Shinji Ikemoto, Yuriy Bashmakov, Joseph L Goldstein, Michael S Brown

Research output: Contribution to journalArticle

618 Citations (Scopus)

Abstract

Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.

Original languageEnglish (US)
Pages (from-to)3182-3194
Number of pages13
JournalGenes and Development
Volume12
Issue number20
StatePublished - Oct 15 1998

Fingerprint

Congenital Generalized Lipodystrophy
Sterol Regulatory Element Binding Protein 1
Adipocytes
White Adipose Tissue
Transgenic Mice
Insulin Resistance
Adipose Tissue
Diabetes Mellitus
Insulin
Complement Factor D
Peroxisome Proliferator-Activated Receptors
Brown Adipose Tissue
Differentiation Antigens
Fatty Liver
Leptin
Blood Glucose
Triglycerides
Parturition
Messenger RNA

Keywords

  • Adipose tissue
  • Congenital generalized lipodystrophy
  • Diabetes mellitus
  • Insulin resistance
  • SREBP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

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title = "Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: Model for congenital generalized lipodystrophy",
abstract = "Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.",
keywords = "Adipose tissue, Congenital generalized lipodystrophy, Diabetes mellitus, Insulin resistance, SREBP",
author = "Iichiro Shimomura and Hammer, {Robert E} and Richardson, {James A} and Shinji Ikemoto and Yuriy Bashmakov and Goldstein, {Joseph L} and Brown, {Michael S}",
year = "1998",
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T1 - Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue

T2 - Model for congenital generalized lipodystrophy

AU - Shimomura, Iichiro

AU - Hammer, Robert E

AU - Richardson, James A

AU - Ikemoto, Shinji

AU - Bashmakov, Yuriy

AU - Goldstein, Joseph L

AU - Brown, Michael S

PY - 1998/10/15

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N2 - Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.

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