Branched fatty acid esters of hydroxy fatty acids (FAHFAs), endogenous lipids influenced by fasting and high-fat diets, are linked to improved insulin sensitivity in mice. These molecules consist of a C-16 or C-18 fatty acid (e.g., palmitoleic, palmitic, oleic, or stearic acid) bonded to a C-16 or C-18 hydroxy fatty acid. A specific FAHFA, 5-POHSA, features palmitoleic acid esterified with hydroxy stearic acid at the 5th carbon. Elevated levels of 5-POHSA in the serum of AG4OX mice, which express high levels of the Glut4 glucose transporter in adipose tissue, correlate with glucose tolerance. Like other FAHFAs that enhance glucose tolerance, stimulate insulin secretion, and exhibit anti-inflammatory properties, 5-POHSA may play a role in managing metabolic syndrome and inflammation.