PMID- 35565866 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220716 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 9 DP - 2022 Apr 30 TI - Distinct AMPK-Mediated FAS/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice. LID - 10.3390/nu14091898 [doi] LID - 1898 AB - Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications. FAU - Xu, Hanyuan AU - Xu H AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Lyu, Xiaorui AU - Lyu X AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Guo, Xiaonan AU - Guo X AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Yang, Hongbo AU - Yang H AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Duan, Lian AU - Duan L AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Zhu, Huijuan AU - Zhu H AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Pan, Hui AU - Pan H AUID- ORCID: 0000-0003-2413-0646 AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Gong, Fengying AU - Gong F AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Wang, Linjie AU - Wang L AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. LA - eng GR - 7222137/Beijing Natural Science Foundation/ GR - 7182130/Beijing Natural Science Foundation/ GR - 2020-N-01-10/China Diabetes Young Scientific Talent Research Project/ GR - 2019-1002-26/Innovation fund for postgraduate students of Peking Union Medical College/ GR - 81370898/National Natural Science Foundation of China/ GR - 30771026/National Natural Science Foundation of China/ GR - 2021-1-I2M-002/CAMS Innovation Fund for Medical Sciences (CIFMS)/ GR - WBYZ2011-873/National Key Program of Clinical Science/ GR - 2013-020/PUMCH Foundation/ PT - Journal Article DEP - 20220430 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Aporphines) RN - 0 (Lipids) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - W26UEB90B7 (nuciferine) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - *Aporphines/adverse effects/metabolism MH - Diet, High-Fat/adverse effects MH - *Fatty Liver/drug therapy/etiology/prevention & control MH - Lipids/pharmacology MH - Liver/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/complications/etiology PMC - PMC9101490 OTO - NOTNLM OT - AMP-activated protein kinase (AMPK) OT - Nuciferine (Nuci) OT - fatty acid synthase (FAS) OT - hepatic steatosis OT - hormone sensitive lipase (HSL) OT - obesity COIS- The authors declare no conflict of interest. EDAT- 2022/05/15 06:00 MHDA- 2022/05/18 06:00 PMCR- 2022/04/30 CRDT- 2022/05/14 01:21 PHST- 2022/03/20 00:00 [received] PHST- 2022/04/23 00:00 [revised] PHST- 2022/04/27 00:00 [accepted] PHST- 2022/05/14 01:21 [entrez] PHST- 2022/05/15 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/04/30 00:00 [pmc-release] AID - nu14091898 [pii] AID - nutrients-14-01898 [pii] AID - 10.3390/nu14091898 [doi] PST - epublish SO - Nutrients. 2022 Apr 30;14(9):1898. doi: 10.3390/nu14091898.