12-pahsa

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified endogenous lipids regulated by fasting and high-fat feeding and associated with insulin sensitivity. Structurally, these esters are comprised of a C-16 or C-18 fatty acid (e.g., palmitoleic, palmitic, oleic, or stearic acid) linked to either a C-16 or C-18 hydroxy substituent. 12-PAHSA is a FAHFA in which palmitic acid is esterified at the 12th carbon of hydroxy stearic acid. Among the FAHFA family members, PAHSAs are the most abundant in the adipose tissue of glucose tolerant AG4OX mice, which overexpress the Glut4 glucose transporter specifically in adipose tissue. 12-PAHSA is present at 2- to 3-fold higher levels in adipose tissue of AG4OX mice compared to wild type mice. Levels of 12-PAHSA are also higher in fasted wild-type mice compared to fed mice and are reduced upon high-fat diet-induced obesity in insulin-resistant mice.

1-Palmitoyl-2-12-PAHSA-3-oleoyl-sn-glycerol, an endogenous triacylglycerol, comprises palmitic acid (at the sn-1 position), the fatty acid ester of hydroxy fatty acids (FAHFA), 12-PAHSA (at the sn-2 position), and oleic acid (at the sn-3 position). Identified in the lipid extract of mouse adipose tissue, this triacylglycerol demonstrates that levels of FAHFA-containing triacylglycerols are over 100-fold higher than those of non-esterified FAHFAs, suggesting their role as intracellular storage reservoirs for FAHFAs.