A recent study similarly showed that the microbe-dependent ω6 linoleic acid metabolite HYA ameliorated metabolic disorders.47 HYA induced GPR40- and GPR120-dependent GLP1 secretion from enteroendocrine cells, facilitated glucose metabolism, and inhibited the development of obesity.47 Therefore, αKetoA and HYA are both microbe-dependent metabolites of essential fatty acids that improve glucose metabolism through the different molecular and cellular bases of the αKetoA–PPARγ axis in macrophages and the HYA–GPR40 and –GPR120 axes in enteroendocrine cells. The gene discussed is FFAR4; the disease is obesity due to melanocortin 4 receptor deficiency.