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Here, we evaluated how the impairment of mitochondrial fusion in hepatocytes affects diet-induced liver steatosis and obesity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Male mice selectively lacking the key protein involved in inner mitochondrial fusion, optic atrophy 1 (OPA1) (OPA1\u0394Hep) were fed a high fat diet (HFD) for 20 weeks. OPA1\u0394Hep mice were protected from the development of hepatic steatosis and obesity because of reduced lipid absorption; a profile which was accompanied by increased respiratory exchange ratio in vivo, suggesting a preference for carbohydrates in OPA1\u0394Hep compared to controls. At the molecular level, this phenotype emerged as a consequence of poor mitochondria-peroxisome- endoplasmic reticulum (ER) tethering in OPA1 deficient hepatocytes, which impaired BAs conjugation and release in the bile, thus impacting lipid absorption from the diet. Concordantly, the liver of subjects with non-alcoholic fatty liver disease (NAFLD) presented an increased expression of OPA1 and of the network of proteins involved in mitochondrial function when compared with controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Patients with NAFLD present increased expression of proteins involved in mitochondrial fusion in the liver. The selective deficency of OPA1 in hepatocytes protects mice from HFD-induced metabolic dysfunction by reducing BAs secretion and dietary lipids absorption as a consequence of reduced liver mitochondria-peroxisome-ER tethering.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad169","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T23:45:14Z","timestamp":1699055114000},"page":"2917-2929","source":"Crossref","is-referenced-by-count":33,"title":["The inhibition of inner mitochondrial fusion in hepatocytes reduces non-alcoholic fatty liver and improves metabolic profile during obesity by modulating bile acid conjugation"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-8689","authenticated-orcid":false,"given":"Lorenzo","family":"Da Dalt","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Moregola","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-7308","authenticated-orcid":false,"given":"Monika","family":"Svecla","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-6321","authenticated-orcid":false,"given":"Silvia","family":"Pedretti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fantini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Ronzio","sequence":"additional","affiliation":[{"name":"Dipartiment of Biosciences, Universit\u00e0 Degli Studi di Milano , Via Celoria 26, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Uboldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Dolfini","sequence":"additional","affiliation":[{"name":"Dipartiment of Biosciences, Universit\u00e0 Degli Studi di Milano , Via Celoria 26, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-5863","authenticated-orcid":false,"given":"Elena","family":"Donetti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science for Health, Universit\u00e0 Degli Studi di Milano , Via Mangiagalli, 31 , 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-1999","authenticated-orcid":false,"given":"Andrea","family":"Baragetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-3619","authenticated-orcid":false,"given":"Nico","family":"Mitro","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 Degli Studi di Milano , Via Balzaretti 9, 20133 Milan , Italy"},{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-8928","authenticated-orcid":false,"given":"Luca","family":"Scorrano","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova , Via U. 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