한빛사논문
- 조회2,754
Abstract
Da Young Oh1,*, Evelyn Walenta1, Taro E Akiyama2, William S Lagakos1, Denise Lackey1, Ariane R Pessentheiner1,3, Roman Sasik1, Nasun Hah4, Tyler J Chi1, Jason M Cox2, Mary Ann Powels2, Jerry Di Salvo2, Christopher Sinz2, Steven M Watkins5, Aaron M Armando6, Heekyung Chung1, Ronald M Evans4,7, Oswald Quehenberger1,6, Joanne McNelis1, Juliane G Bogner-Strauss3 & Jerrold M Olefsky1,*
1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2Merck Research Laboratories, Kenilworth, New Jersey, USA. 3Institute of Biochemistry, Graz University of Technology, Graz, Austria. 4Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA. 5Lipomics Technologies, West Sacramento, California, USA. 6Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. 7Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California, USA.
*Correspondence to: Da Young Oh or Jerrold M Olefsky
It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects1, 2, 3, 4. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity5, 6, 7. We reported that Gpr120 is the functional receptor for these fatty acids and that ω?3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner8. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4)9. However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor10, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future.
논문정보
- Research article
- 2014년 07월 (BRIC 등록일 2014-07-10)
- 국외 연구진
- 생명과학 > 세포생물학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
