Increased Fatty Acid Oxidation Protects Against Development of Metabolic Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition characterized by fat accumulation in the liver, affects over 30% of Americans. Development of fatty liver is attributed to poor diet, lack of exercise, and liver metabolic dysfunction. We found that liver fatty acid oxidative (FAO) metabolism increases during the initiation of fatty liver disease. FAO is the key pathway to harness energy from fats; however, dysregulation of FAO is thought to contribute to numerous metabolic diseases. Here, we questioned whether the contribution of increased FAO was protective or detrimental towards the development of MASLD. To do so, we generated a novel conditional mouse model of liver specific deletion of carnitine-acylcarnitine translocase (Cact), a required and nonhomologous enzyme in the FAO pathway (Cact Liv-/-). MASLD was initiated with a fatty-liver diet feeding for 1 week in control and CACT Liv-/-, and tissues were collected for RNA extraction, respirometry, and pathology analysis. CACT Liv-/- mice display a more severe MASLD phenotype, suggesting that increased liver FAO capacity is protective against MASLD pathology. R01: DK125812 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.