{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:18:46Z","timestamp":1773818326723,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81672834"],"award-info":[{"award-number":["81672834"]}]},{"name":"National Natural Science Foundation of China","award":["81272406"],"award-info":[{"award-number":["81272406"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The roles of lamin A\/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that LMNA knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A\/C levels at serine 22 or 392 sites (pLamin A\/C-S22\/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells). Moreover, HCC cells did not survive after LMNA knockout (KO) or even KD. Evidently, the functions of lamin A\/C differ between the liver and adipose tissue. To date, the mechanism of hepatocyte lipid metabolism mediated by nuclear lamin A\/C remains unclear. Our in-depth study aimed to identify the molecular connection between lamin A\/C and pLamin A\/C, hepatic lipid metabolism and liver cancer. Gain- and loss-of-function experiments were performed to investigate functional changes and the related molecular pathways in 7701 cells. Adenosine 5\u2019 monophosphate-activated protein kinase \u03b1 (AMPK\u03b1) was activated when abnormalities in functional lamin A\/C were observed following lamin A\/C depletion or farnesyltransferase inhibitor (FTI) treatment. Active AMPK\u03b1 directly phosphorylated acetyl-CoA-carboxylase 1 (ACC1) and subsequently inhibited lipid synthesis but induced glycolysis in both HCC cells and normal cells. According to the mass spectrometry analysis, lamin A\/C potentially regulated AMPK\u03b1 activation through its chaperone proteins, ATPase or ADP\/ATP transporter 2. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of the two HCC cell lines more efficiently than lonafarnib alone by inhibiting glycolysis or the maturation of prelamin A.<\/jats:p>","DOI":"10.3390\/cells11243988","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T03:36:09Z","timestamp":1670816169000},"page":"3988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Loss of Mature Lamin A\/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPK\u03b1 Activation"],"prefix":"10.3390","volume":"11","author":[{"given":"Ying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Physiology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge-Xuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-9666","authenticated-orcid":false,"given":"Rong-Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"The Central Laboratory for Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Friendship Hospital, The Second Clinical Medical College of Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4998-1327","authenticated-orcid":false,"given":"Lu","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.2741\/216","article-title":"A-type lamins and Hutchinson-Gilford progeria syndrome: Pathogenesis and therapy","volume":"3","author":"Gonzalez","year":"2011","journal-title":"Front Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1083\/jcb.151.6.1155","article-title":"Nuclear lamins A and B1: Different pathways of assembly during nuclear envelope formation in living cells","volume":"151","author":"Moir","year":"2000","journal-title":"J. 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