Mice overexpressing the glucose transporter Glut4 in adipocytes (AG4OX mice) exhibit elevated lipogenesis and increased glucose tolerance, despite being obese with elevated circulating fatty acids. Yore et al. identified elevated levels of novel metabolically beneficial branched fatty acid esters of hydroxy fatty acids (FAHFA) in adipose tissue (AT) from AG4OX compared with wild-type mice. The most highly upregulated FAHFAs in AG4OX AT were palmitic acid-hydroxy stearic acids (PAHSAs), which signal through GPR120. In humans, PAHSA levels correlated with insulin sensitivity, and in mice PAHSA administration lowered glycaemia, improved glucose tolerance and stimulated GLP-1 and insulin secretion.
References
Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014)
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Crunkhorn, S. New lipid class regulates glucose homeostasis. Nat Rev Drug Discov 13, 888 (2014). https://doi.org/10.1038/nrd4501
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DOI: https://doi.org/10.1038/nrd4501
