Oleic acid promotes lipid accumulation in bovine adipocytes: the role of peroxisome proliferator-activated receptor alpha (PPARα) signaling

Excessive lipid mobilization due to negative energy balance in periparturient dairy cows increases their risk for diseases and decreases their productivity, highlighting the importance of enhancing energy availability during the immediate postpartum to limit negative energy balance. Oleic acid (OA) supplementation increases the energy density of the diet and holds promise in addressing metabolic challenges. In periparturient cows, OA limits lipolysis and improves adipose tissue (AT) insulin sensitivity. However, the mechanisms behind these effects are still unknown. Our objective was to characterize the effects of OA, alone and in combination with palmitic acid (PA), on lipogenic function and identify a mechanism of action in bovine adipocytes. We hypothesized that OA enhances lipid accumulation in bovine adipocytes via peroxisome proliferator-activated receptor alpha (PPARα)-dependent activation of lipogenic pathways. Pre-adipocytes were isolated from AT of Holstein dairy cows and induced to differentiate into adipocytes. Mature adipocytes were cultured with standard differentiation media (CON) supplemented with PA or OA (100, 200, and 300 µM), and mixtures of PA-OA (60-40, 50-50, and 40-60 ratios at 300 µM) for 4 or 7 d. To evaluate the effect of PPARα signaling, adipocytes were treated with or without a PPARα-specific antagonist (GW6471; 10 µM) for 7 d after induction. Compared with CON, fatty acid treatments had no effect on preadipocyte differentiation (P = 0.65). The treatments 300PA, 200OA, 300OA, 60-40, 50-50, and 40-60 increased lipid accumulation compared with CON (P < 0.0001). At d 4, 300PA and 300OA increased PPARα protein expression compared with CON (P = 0.04). PPARα inhibition decreased triglyceride levels in OA and 60-40 (P < 0.05) but not in PA (P = 0.26). Our results show a direct effect of OA supplementation on bovine adipocyte metabolism, resulting in lipid accumulation, mainly through PPARα signaling, which in turn activates lipogenic networks. Hence, providing mechanistic evidence for the use of OA, along with PA, in dairy cow diets during the periparturient period to enhance lipid accumulation and limit lipolysis. Improving energy balance will ultimately minimize health disorders and improve the production of early postpartum cows.