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

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. Furthermore, inhibiting ER stress using 4-PBA also inhibited lipolysis and alleviated DHA-induced activation of the cAMP/PKA signaling pathway, suggesting that ER stress may participate in DHA-induced lipolysis through the activation of the cAMP/PKA signaling pathway. Our data illustrate that DHA supplementation can be a promising nutritional strategy for ameliorating lipid accumulation in grass carp. The present study elucidated the molecular mechanism for DHA-induced lipolysis in grass carp adipocytes and emphasized the importance of ER stress and the cAMP/PKA pathway in DHA-induced lipolysis. These results deepen our understanding of ameliorating lipids deposition in freshwater fish by targeting DHA.

 

Comments:

The passage you provided describes a study that investigated the effect of docosahexaenoic acid (DHA) on lipolysis, the breakdown of fats, in grass carp (Ctenopharyngodon idella). The researchers aimed to understand the molecular mechanisms underlying DHA-induced lipolysis and its potential role in reducing lipid accumulation in fish.

The study found that DHA supplementation significantly reduced the triglyceride content and promoted lipolysis in adipocytes (fat cells) of grass carp. It also increased the secretion of glycerol, a product of lipolysis. The researchers observed that DHA treatment induced endoplasmic reticulum (ER) stress, which activates a cellular response called the unfolded protein response. This response has been linked to lipid metabolism.

To further investigate the role of ER stress in DHA-induced lipolysis, the researchers used a chemical called 4-phenyl butyric acid (4-PBA) to inhibit ER stress. They found that inhibiting ER stress with 4-PBA diminished the effects of DHA on lipolysis, suggesting that ER stress is involved in DHA-induced lipolysis.

The study also focused on a specific component of the unfolded protein response called inositol-requiring enzyme 1α (IRE1α) and its associated protein, X-box binding protein 1 (XBP1). They discovered that inhibiting IRE1α using a specific inhibitor called STF-083010 attenuated the effects of DHA on lipolysis, indicating that IRE1α and XBP1 may play a role in DHA-induced lipolysis.

Furthermore, the researchers explored the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, which is known to be involved in lipolysis. They observed that DHA supplementation increased the levels of cAMP and activated the PKA enzyme. Inhibiting PKA using an inhibitor called H89 weakened the lipolytic effects of DHA, suggesting that the cAMP/PKA pathway is necessary for DHA-induced lipolysis.

Interestingly, inhibiting ER stress with 4-PBA also inhibited lipolysis and alleviated DHA-induced activation of the cAMP/PKA pathway. This suggests that ER stress may be involved in DHA-induced lipolysis by activating the cAMP/PKA signaling pathway.

Overall, the study provides insights into the molecular mechanisms underlying DHA-induced lipolysis in grass carp adipocytes. It highlights the importance of ER stress and the cAMP/PKA pathway in mediating the effects of DHA on lipolysis. These findings contribute to a better understanding of how DHA supplementation can potentially reduce lipid accumulation in freshwater fish like grass carp.