SREBP-1c and Elovl6 as Targets for Obesity-related Disorders

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Hitoshi Shimano

Abstract

Recent studies suggest that chronic local inflammation and cellular stresses are the key steps in organ defects in obesity-related diseases such as atherosclerosis, diabetes, and fatty liver. We have shown that an excess energy state activates sterol regulatory element-binding protein (SREBP)-1c, a master transcription factor for fatty acid synthesis causing the accumulation of lipids leading to fatty liver, insulin resistance, insulin secretion defects, and dyslipidemia and we clarified their molecular mechanisms. Recently, we shifted focus to the quality aspect of accumulated lipids. It has long been known that saturated and poly-unsaturated fatty acids are atherogenic and anti-atherogenic, respectively. Besides desaturation, we found that the chain-length of fatty acids is another important factor. Elovl6 that we have cloned as an SREBP-1 target is a fatty acid elongase that catalises the last step of fatty acid synthesis. Elovl6 KO mice exhibit obesity and fatty liver on a high energy diet, but unexpectedly were immune to insulin resistance (Nat. Med., 13, 2007, Matsuzaka et al.), atherosclerosis (Arterioscler. Thromb. Vasc. Biol., 31, 2011, Saito et al.) and non-alcoholic steatohepatitis (NASH) pathology including liver da...Continue Reading

References

Jul 27, 2000·The Journal of Biological Chemistry·A H HastyN Yamada
Aug 5, 2000·The Journal of Biological Chemistry·M Amemiya-KudoN Yamada
Mar 30, 2004·Nature Cell Biology·Tomohiro IdeNobuhiro Yamada
Jan 29, 2005·Diabetes·Akimitsu TakahashiHitoshi Shimano
Jan 16, 2009·The FEBS Journal·Hitoshi Shimano
Mar 5, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Takashi Matsuzaka, Hitoshi Shimano
Jul 4, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Takashi MatsuzakaHitoshi Shimano
Oct 12, 2013·Nature Communications·Hiroaki SunagaMasahiko Kurabayashi

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