PL05-01 - Biology and Therapeutic Potential of a Class of Lipids with Beneficial Actions for both Type 1 and Type 2 Diabetes

Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs) are bioactive lipids that are made in humans, animals, plants and lower organisms, including yeast. FAHFAs are present in all mammalian tissues with highest concentrations in adipose tissue. FAHFAs consist of a fatty acid and a hydroxy fatty acid bound by an ester bond. There are hundreds of FAHFAs that vary by carbon number and ester bond position. Several FAHFAs including palmitic acid hydroxy stearic acids (PAHSAs) are insulin-sensitizing, potentiate glucose-stimulated insulin secretion, and have anti-inflammatory and anti-oxidant properties. These protective effects of PAHSAs delay the onset and reduce the severity of colitis and markedly reduce the incidence of auto-immune type 1 diabetes in mice by maintaining pancreatic beta cell mass. The mechanism is, at least in part, prevention of cellular senescence, an effect which PAHSAs exert also in human islets under metabolic stress. In people, serum and adipose tissue PAHSA levels correlate highly with insulin sensitivity and a fall in PAHSAs over time predicts worsening glucose tolerance. This talk will discuss our recent discoveries of the molecular regulation of these beneficial signaling lipids and their therapeutic potential for both type 1 and type 2 diabetes.