Figure 8.

Summary of biologic activities of FAHFAs. Increased GLUT4 protein levels in adipocytes results in increased de novo lipogenesis driven by ChREBP. This results in the production of FAHFAs, which act through GPCRs (GPR-120) to augment glucose transport and GLUT4 translocation. These lipids also decrease inflammatory responses in macrophages and dendritic cells. In aged, insulin-resistant chow-fed mice (but not in high-fat diet [HFD]–fed mice), these lipids increase glucose-stimulated GLP1 secretion and insulin secretion. FAHFAs directly increase insulin secretion in human pancreatic β-cells, which involves GPR-40. As we do not see these secretory effects of the novel lipids in mice on an HFD but find increased insulin sensitivity with chronic PAHSA treatment, it is likely that insulin-sensitizing effects of the PAHSAs play a major role in their beneficial effects in HFD-fed mice. Adapted from Yore et al. (30). BAT, brown adipose tissue.