Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets

Tetsuya Kakuma, Young Lee, Moritake Higa, Zhuo Wei Wang, Wentong Pan, Iichiro Shimomura, Roger H. Unger

Research output: Contribution to journalArticle

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Abstract

Overaccumulation of lipids in nonadipose tissues of obese rodents may lead to lipotoxic complications such as diabetes. To assess the pathogenic role of the lipogenic transcription factor, sterol regulatory element binding protein 1 (SREBP-1), we measured its mRNA in liver and islets of obese, leptin-unresponsive fa/fa Zucker diabetic fatty rats. Hepatic SREBP-1 mRNA was 2.4 times higher than in lean +/+ controls, primarily because of increased SREBP-1c expression. mRNA of lipogenic enzymes ranged from 2.4- to 4.6-fold higher than lean controls, and triacylglycerol (TG) content was 5.4 times higher. In pancreatic islets of fa/fa rats, SREBP-1c was 3.4 times higher than in lean +/+ Zucker diabetic fatty rats. The increase of SREBP-1 in liver and islets of untreated fa/fa rats was blocked by 6 weeks of troglitazone therapy, and the diabetic phenotype was prevented. Upregulation of SREBP-1 also occurred in livers of Sprague-Dawley rats with diet-induced obesity. Hyperleptinemia, induced in lean +/+ rats by adenovirus gene transfer, lowered hepatic SREBP-1c by 74% and the lipogenic enzymes from 35 to 59%. In conclusion, overnutrition increases and adenovirus-induced hyperleptinemia decreases SREBP-1c expression in liver and islets. SREBP-1 overexpression, which is prevented by troglitazone, may play a role in the ectopic lipogenesis and lipotoxicity complicating obesity in Zucker diabetic fatty rats.

Original languageEnglish (US)
Pages (from-to)8536-8541
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number15
DOIs
StatePublished - Jul 18 2000
Externally publishedYes

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troglitazone
Sterol Regulatory Element Binding Proteins
Sterol Regulatory Element Binding Protein 1
Leptin
Islets of Langerhans
Liver
Adenoviridae
Messenger RNA
Obesity
Overnutrition
Lipogenesis
Enzymes

ASJC Scopus subject areas

  • General

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Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. / Kakuma, Tetsuya; Lee, Young; Higa, Moritake; Wang, Zhuo Wei; Pan, Wentong; Shimomura, Iichiro; Unger, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 15, 18.07.2000, p. 8536-8541.

Research output: Contribution to journalArticle

Kakuma, Tetsuya ; Lee, Young ; Higa, Moritake ; Wang, Zhuo Wei ; Pan, Wentong ; Shimomura, Iichiro ; Unger, Roger H. / Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 15. pp. 8536-8541.
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