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Adenosine monophosphate\u2010activated protein kinase (AMPK) is a cellular energy sensor and regulator of liver lipid dysfunction and glucose metabolism. The mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. Together, these pathways are involved in obesity, insulin resistance, non\u2010alcoholic fatty liver disease (NAFLD) and its progression, and autophagy. During energy demand, liver kinase B (LKB) phosphorylation helps activate the AMPK\/mTOR pathways. Likewise, the protein forkhead box O family (FOXO) negatively regulates adipogenesis by binding to the promoter sites of peroxisome proliferator\u2010activated receptor\u2010gamma coactivator 1\u2010alpha, initiating adipogenesis. In addition, acetyl\u2010CoA carboxylase, which regulates de novo lipogenesis, is linked to LKB and FOXO in developing NAFLD. The kinase complex, consisting of Unc\u201051\u2010like autophagy\u2010activating kinase 1 or 2 (ULK1, ULK2) by stimulating autophagy, and eliminating fat droplets in NAFLD, is regulated by mTORC1 and negatively regulated by AMPK that suppresses liver lipogenesis and increases fatty acid oxidation. Also, ULK1 is essential for initiating phagophore formation, establishing macrophagy, and generating autophagosomes. The selective breakdown of lipid droplets through macroautophagy, or macrolipophagy, occurs on a cellular energy level using free fatty acids. In addition, mTORC1 promotes lipogenesis by activating sterol regulatory element\u2010binding protein. Finding new components and novel regulatory modes in signaling is significant for a better understanding of the AMPK\/mTOR pathways, potentially facilitating the development of future diagnostic and therapeutic strategies for NAFLD and its progression to non\u2010alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma.<\/jats:p>","DOI":"10.1111\/jgh.16272","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:14:17Z","timestamp":1689207257000},"page":"1868-1876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["AMPK\/mTOR pathway significance in healthy liver and non\u2010alcoholic fatty liver disease and its progression"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-4033","authenticated-orcid":false,"given":"Ilitch Aquino","family":"Marcondes\u2010de\u2010Castro","sequence":"first","affiliation":[{"name":"Laboratory of 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