Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects.

Published

Journal Article

Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.

Full Text

Duke Authors

Cited Authors

  • Yore, MM; Syed, I; Moraes-Vieira, PM; Zhang, T; Herman, MA; Homan, EA; Patel, RT; Lee, J; Chen, S; Peroni, OD; Dhaneshwar, AS; Hammarstedt, A; Smith, U; McGraw, TE; Saghatelian, A; Kahn, BB

Published Date

  • October 2014

Published In

Volume / Issue

  • 159 / 2

Start / End Page

  • 318 - 332

PubMed ID

  • 25303528

Pubmed Central ID

  • 25303528

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.09.035

Language

  • eng