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This study aimed to investigate whether the activity of mTOR complex 2 (mTORC2) affects the progression of HP and its underlying mechanisms. In vivo, a high\u2010fat diet and retrograde administration of sodium taurocholate were employed to establish the\u00a0HP models in rats, with pancreatic tissue pathology evaluated. The expression of Rictor and peroxisome proliferator\u2010activator receptor (PPAR) was examined. The serum levels of TG, fatty acid metabolites, inflammatory and lipid metabolism\u2010related factors were determined. In vitro, pancreatic acinar cells (PACs) were exposed to palmitic acid and cholecystokinin\u20108. PAC apoptosis, pyroptosis, and ferroptosis were assessed. In the HP models, rats and PACs exhibited upregulated Rictor and downregulated PPAR\u03b1, and Rictor knockdown promoted PPAR\u03b1 expression. In vivo, Rictor knockdown decreased the serum levels of TG, \u03b1\u2010amylase, total cholesterol, low\u2010density lipoprotein cholesterol, lactate dehydrogenase, and inflammatory factors, while increasing high\u2010density lipoprotein cholesterol levels. Rictor knockdown increased ACOX1 and CPT1\u03b1 and decreased SREBP\u20101, CD36, SCD1, ACLY, and ACACA. Rictor knockdown reduced damage to pancreatic tissue structure. In vitro, Rictor knockdown inhibited PAC apoptosis, pyroptosis, and ferroptosis. Treatment with the PPAR\u03b1 antagonist GW6471 abolished the beneficial effects of Rictor knockdown. Rictor\/mTORC2 deficiency reduces serum TG levels, maintains lipid homeostasis, and suppresses inflammation by inhibiting PPAR\u03b1 expression. Weakening mTORC2 activity holds promise as a novel therapeutic strategy for HP.<\/jats:p>","DOI":"10.1002\/jbt.23802","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T11:13:55Z","timestamp":1723461235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["mTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPAR\u03b1"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-2492","authenticated-orcid":false,"given":"Xiangyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hunan Provincial People's Hospital The First Affiliated Hospital of Hunan Normal University  Changsha 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