T. Kakuma et al., Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets, P NAS US, 97(15), 2000, pp. 8536-8541
Citations number
32
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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 pr
otein 1 (SREBP-1). we measured its mRNA in liver and islets of obese, lepti
n-unresponsive fa/fa Zucker diabetic fatty rats. Hepatic SREBP-1 mRNA was 2
.4 times higher than in lean +/+ controls, primarily because of increased S
REBP-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 h
igher. In pancreatic islets of fa/fa rats, SREBP-1c was 3.4 times higher th
an 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. H
yperleptinemia, induced in lean +/+ rats by adenovirus gene transfer, lower
ed hepatic SREBP-1c by 74% and the lipogenic: enzymes from 35 to 59%. In co
nclusion, overnutrition increases and adenovirus-induced hyperleptinemia de
creases SREBP-1c expression in liver and islets. SREBP-1 overexpression, wh
ich is prevented by troglitazone, may play a role in the ectopic lipogenesi
s and lipotoxicity complicating obesity in Zucker diabetic fatty rats.