Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats

• DOI: 10.1073/pnas.0401715101
• Publication Date: 2004-04-20T00:56:12Z
• Authors: Kiyosumi Takaishi; Laurence Duplomb; May-Yun Wang; Jinping Li; Roger H. Unger
• Keywords: Lipogenesis; Steatosis; Hyperlipidemia

To determine whether the antilipogenic actions of insulin-induced gene 1 (insig-1) demonstrated in cultured preadipocytes also occur vivo, we infected Zucker diabetic fatty (ZDF) (fa/fa) rats, with recombinant adenovirus containing insig-1 or -2 cDNA. An increase both proteins appeared their livers. In control ZDF rats beta-galactosidase (beta-gal) cDNA, triacylglycerols liver and plasma rose steeply whereas insig-infected exhibited substantial attenuation hepatic steatosis hyperlipidemia. Insig overexpression was associated a striking reduction elevated level nuclear sterol regulatory element-binding protein (SREBP)-1c, activated form transcription factor. The mRNA SREBP-1c lipogenic target enzymes fell. endogenous insig-1, but not -2a -2b, higher livers untreated obese compared controls, elevation sufficient to block approximately 3-fold expression activity. normal animals, adenovirus-induced insigs reduced its caused by refeeding. findings that have action when transgenically overexpressed increased SREBP-1c-mediated lipogenesis. However, augmented lipogenesis may limit it, is insufficient prevent it.