Dehydroepiandrosterone alleviates oleic acid-induced lipid metabolism disorders through activation of AMPK-mTOR signal pathway in primary chicken hepatocytes

The incident of lipid metabolism disorders has obviously increased under the undue pursuit of effi-ciency, which had seriously threatened to the health devel-opment of poultry industry. As an important cholesterol-derived intermediate, though dehydroepiandrosterone (DHEA) has the fat-reduction effect in animals and humans, but the underlying mechanism still poorly under-stood. Herein, the present study aimed to investigate the regulatory effects and its molecular mechanism of DHEA on disturbance of lipid metabolism induced by oleic acid (OA) in primary chicken hepatocytes. The hepatocytes were treated with 0, 0.1, 1, 10 mM DHEA for 4 h, and then supplemented with 0 or 0.5 mM OA stimulation for another 24 h. Our findings demonstrated that DHEA treatment effectively reduced TG content and alleviated lipid droplet deposition in OA-induced hepatocytes. DHEA inhibited the lipogenesis related factors (ACC, FAS, SREBP-1c, and ACLY) mRNA level and increased the lipolysis key factors (CPT-1 and PPARa) mRNA levels. In addition, DHEA obviously elevated the protein levels of CPT-1A, p-ACC, and ECHS1; whereas decreased the protein levels of FAS and SREBP-1 in hepatocytes stimulated by OA. Furthermore, DHEA promoted the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mamma-lian target of rapamycin (mTOR). Mechanistically, the hepatocytes were pre-treated with AMPK inhibitor com-pound C or AMPK activator AICAR before addition of DHEA treatment, and the results certified that DHEA activated cAMP/AMPK pathway and which subse-quently led the inhibition of mTOR signal, which finally reduced the fat excessive accumulation in OA-stimulated hepatocytes. Collectively, our study unveiled that DHEA protects against the lipid metabolism disorders triggered by OA stimulation through activation of AMPK-mTOR signaling pathway, which prompts the value of DHEA as a potential nutritional supplement in regulating the lipid metabolism and its related disease in poultry.

Automated summary

The incident of lipid metabolism disorders has increased under the undue pursuit of efficiency, which seriously threatens the health development of poultry industry. Dehydroepiandrosterone (DHEA), an important cholesterol-derived intermediate, has shown fat-reduction effect, but its mechanism is still poorly understood. This study found that DHEA effectively reduced lipid content and deposition in chicken hepatocytes stimulated by oleic acid (OA) by inhibiting lipogenesis and promoting lipolysis, and activated the AMPK-mTOR signaling pathway to prevent fat excessive accumulation.