PMID- 36565630 OWN - NLM STAT- MEDLINE DCOM- 20230206 LR - 20230206 IS - 1525-3171 (Electronic) IS - 0032-5791 (Print) IS - 0032-5791 (Linking) VI - 102 IP - 2 DP - 2023 Feb TI - Dehydroepiandrosterone alleviates oleic acid-induced lipid metabolism disorders through activation of AMPK-mTOR signal pathway in primary chicken hepatocytes. PG - 102385 LID - S0032-5791(22)00679-4 [pii] LID - 10.1016/j.psj.2022.102385 [doi] LID - 102385 AB - The incident of lipid metabolism disorders has obviously increased under the undue pursuit of efficiency, which had seriously threatened to the health development 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 understood. 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 muM 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 PPARalpha) 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 mammalian target of rapamycin (mTOR). Mechanistically, the hepatocytes were pre-treated with AMPK inhibitor compound C or AMPK activator AICAR before addition of DHEA treatment, and the results certified that DHEA activated cAMP/AMPK pathway and which subsequently 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. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yao, Yao AU - Yao Y AD - Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. FAU - Yang, Ying AU - Yang Y AD - Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. FAU - Wang, Huihui AU - Wang H AD - Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. FAU - Jiang, Zhihao AU - Jiang Z AD - Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. FAU - Ma, Haitian AU - Ma H AD - Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: mahaitian@njau.edu.cn. LA - eng PT - Journal Article DEP - 20221206 PL - England TA - Poult Sci JT - Poultry science JID - 0401150 RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 459AG36T1B (Dehydroepiandrosterone) RN - EC 2.7.1.1 (MTOR protein, human) RN - 2UMI9U37CP (Oleic Acid) RN - 0 (RNA, Messenger) RN - W36ZG6FT64 (Sirolimus) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *AMP-Activated Protein Kinases/metabolism MH - Chickens/genetics MH - Dehydroepiandrosterone/pharmacology/metabolism MH - Hepatocytes MH - Lipid Metabolism MH - *Lipid Metabolism Disorders/metabolism/veterinary MH - Mammals/genetics MH - Oleic Acid/pharmacology/metabolism MH - RNA, Messenger/genetics MH - Signal Transduction MH - Sirolimus MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC9800306 OTO - NOTNLM OT - AMPK signaling pathway OT - Dehydroepiandrosterone OT - hepatocytes OT - lipid metabolism disorders EDAT- 2022/12/25 06:00 MHDA- 2023/02/02 06:00 PMCR- 2022/12/06 CRDT- 2022/12/24 18:21 PHST- 2022/03/11 00:00 [received] PHST- 2022/11/05 00:00 [revised] PHST- 2022/12/01 00:00 [accepted] PHST- 2022/12/25 06:00 [pubmed] PHST- 2023/02/02 06:00 [medline] PHST- 2022/12/24 18:21 [entrez] PHST- 2022/12/06 00:00 [pmc-release] AID - S0032-5791(22)00679-4 [pii] AID - 102385 [pii] AID - 10.1016/j.psj.2022.102385 [doi] PST - ppublish SO - Poult Sci. 2023 Feb;102(2):102385. doi: 10.1016/j.psj.2022.102385. Epub 2022 Dec 6.