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

By M. Yore, I. Syed, Pedro M. Moraes-Vieira, Tejia Zhang, M. Herman, E. Homan, Rajesh T. Patel, Jennifer Lee, Shili Chen, O. Peroni and 6 more. Cell, 2014

750 citations recorded by the source corpus.

Summary 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 16–18-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 GPR-120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.

Subfields: Biochemistry, Nutrition and Dietetics, Surgery

View Paper: https://www.semanticscholar.org/paper/33af098a10a6c33e9aae995624775ea282ce73a4

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In Biochemistry

1. Gerald I. Shulman
2. V. Samuel
3. P. Seale
4. R. Medzhitov
5. M. Kotas

In Surgery

1. Gerald I. Shulman
2. V. Samuel
3. R. Medzhitov
4. M. Kotas

Citations in the corpus

• The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. (2016, background): “Recently, ChREBP was implicated in the synthesis of fatty acid esters of hydroxy fatty acids (FAHFAs), which improve glucose tolerance (89).”
• Adipose tissue plasticity in health and disease (2022, background): “Additionally, DNL in adipocytes results in the production of several lipid species with anti-inflammatory and insulin-sensitizing effects (Yilmaz et al., 2016; Yore et al., 2014).”