SAT112 Ad Libitum Ketogenic Diet Reverts WD-pathological Effects In Liver, But Not In Skeletal Muscle In Mice

Abstract Disclosure: A. Antonioli: None. A. Provera: None. S. Reano: None. L. Gadipudi: None. S. Tini: None. I. Zaggia: None. T. Raiteri: None. A. Scircoli: None. A. Colasanto: None. D. Raineri: None. N. Filigheddu: None. S. Sutti: None. F. Prodam: None. Western diet (WD), rich in sugars and saturated fats, is a critical factor contributing to obesity and its comorbidities. Since its effects on insulin resistance and inflammation, WD has been associated with many diseases, such as type 2 diabetes mellitus (T2DM), metabolic fatty liver disease (MAFLD) and steatohepatitis (NASH), and metabolic syndrome (MetS) in both animal and humans. Ketogenic diets (KDs) are nutritional regimens characterized by very low carbohydrate intake, high-fat amounts, and adequate protein content, with or without caloric restriction. Energy is provided by ketone bodies from lipid oxidation and protein metabolism. Since growing evidence suggests that KDs are able to reduce inflammation, oxidative stress, and improving mitochondrial function, we hypothesized that it could be a promising strategy to treat obesity related diseases, including MAFLD and sarcobesity. To demonstrate these effects, after 16 weeks of WD diet, we switched mice to standard diet (SD), ad libitum cholesterol-free KD, or maintained in WD for further 2 and 4 weeks. We demonstrated that both KD and SD are able to revert detrimental effects induced by WD in mouse liver, improving the pathological features and lowering the hepatic inflammatory responses associated with NASH. KD resulted in ketosis and mimicked fasting conditions promoting body weight loss and glycaemic control. However, KD did not have positive effects on skeletal muscle strength, mass, and histologic morphology after WD-induced muscle atrophy. Despite the positive effect on WD-induced liver damage and increased body weight, ad libitum KD does not seem to have protective effects against WD-associated loss of muscle mass and functionality. However, we cannot rule out that muscle might need a longer recovery period than the liver. Presentation: Saturday, June 17, 2023