Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPAR-Dependent AMPK Activation

Background: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor- (PPAR), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPAR remain unknown. Objective: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. Methods: C57BL6 and PPAR knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Results: Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPAR. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPAR KO mice. Conclusions: In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPAR. J. Cell. Physiol. 232: 2168-2177, 2017. (c) 2016 Wiley Periodicals, Inc.