Phytanic acid activates PPARα to promote beige adipogenic differentiation of preadipocytes.

A better understanding of the mechanisms of beige and brown adipogenesis is needed for developing strategies to prevent and treat obesity and associated metabolic disorders. Phytanic acid (PA) exists in a wide range of foods, especially in milk fat and marine foods, but its effects on obesity and beige adipogenesis remain poorly defined. The objective is to investigate the effects and regulatory mechanisms of PA in the beige adipogenesis. In 3T3-L1 preadipocytes, PA elevated the expression of brown adipogenic markers, suggesting that PA promotes beige adipogenic differentiation in committed adipogenic cells. In uncommitted C3H10T1/2 cells, while PA increased PGC1α expression, it did not increase brown adipogenic regulators PRDM16 or UCP1 expression, suggesting that PA had no significant effects on brown adipocyte commitment. PA also enhanced mitochondrial biogenesis and oxygen consumption. Promotion of both mitochondriogenesis and beige adipogenic differentiation were blocked by using PPARα antagonist or with Pparα knockdown, showing that PA-mediated beige/brown adipogenic differentiation is dependent on PPARα. Additionally, the PA-regulated effect is independent on β3-adrenergic receptor. Taken together, PA promotes beige adipogenic differentiation, but not the commitment of progenitor cells to the brown adipocyte lineage. PPARα is a key mediator during PA-induced beige/brown adipogenic differentiation.