RT Journal Article SR Electronic T1 Oleoylethanolamide increases glycogen synthesis and inhibits hepatic gluconeogenesis via the LKB1/AMPK pathway in type 2 diabetic model JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.119.262675 DO 10.1124/jpet.119.262675 A1 Tong Ren A1 Ang Ma A1 Rengong Zhuo A1 Huaying Zhang A1 Lu Peng A1 Xin Jin A1 Enhui Yao A1 Lichao Yang YR 2020 UL http://jpet.aspetjournals.org/content/early/2020/02/05/jpet.119.262675.abstract AB Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via LKB1/AMPK signalling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its anti-diabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/ AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM.SIGNIFICANCE STATEMENT 1. OEA exerted a potent anti-hyperglycaemic effect in a PPARα-independent manner; 2. OEA played an anti-hyperglycaemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis; 3. The main molecular mechanism of OEA in regulating liver glycometabolism is activation of the LKB1/AMPK signalling pathway.