DHA induces adipocyte lipolysis through endoplasmic reticulum stress and the cAMP/PKA signaling pathway in grass carp (Ctenopharyngodon idella)

作者：Xiaocheng Huang, Chenchen Bian, Hong Ji, Shanghong Ji, Jian Sun · 发表于：Animal nutrition · 年份：2022 · DOI：10.1016/j.aninu.2022.10.010 · 被引用次数：26 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Calpain Protease Function and Regulation

Docosahexaenoic acid (DHA) is a biologically active fatty acid that reduces the accumulation of lipids. However, the molecular mechanism underlying this process, particularly in fish, is not well understood. Recent studies show that endoplasmic reticulum (ER) stress triggers the activation of the unfolded protein response, which has been revealed to play an essential role in lipid metabolism. In this study, we explored the effect of DHA on ER stress and investigated the potential molecular mechanisms underlying DHA-induced adipocyte lipolysis in grass carp (Ctenopharyngodon idella) both in vivo and in vitro. We found that DHA remarkably reduced the triglyceride content, increased the secretion of glycerol, promoted lipolysis in adipocytes and evoked ER stress, whereas inhibiting ER stress using 4-phenyl butyric acid (4-PBA) inhibited the effects of DHA (P < 0.05). These results implied that ER stress potentially participates in DHA-induced adipocyte lipolysis. Additionally, STF-083010, a specific inositol-requiring enzyme 1α (IRE1α)-inhibitor, attenuated the effects of DHA on lipolysis, demonstrating that IRE1α and X-box binding protein 1 potentially participate in DHA-induced lipolysis. DHA also activated the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway by increasing the level of cAMP and activating the PKA enzyme (P < 0.05). Nevertheless, H89, a PKA inhibitor, weakened DHA-induced lipolysis by inhibiting the cAMP/PKA signaling pathway. Furt...