NODES_INNDIANA_Z113_Double-Edge Sword of Ketogenic Diet: Hepatic Improvement at the Expense of Musculoskeletal Health

Oral presentation at the IIM Congress 2025. The Western diet (WD), rich in sugars and saturated fats, is strongly linked to obesity, insulin resistance, and inflammation, contributing to conditions such as type 2 diabetes, cardiovascular diseases, and MASLD. Ketogenic diets (KDs), characterized by low carbohydrate intake and increased reliance on ketone bodies for energy, have been proposed as a potential strategy to counteract these effects. In our study, mice were fed a WD for 16 weeks and then either switched to a KD or maintained on WD. The switch to KD produced contrasting outcomes across different tissues: it improved liver health by reducing steatosis, inflammation, and fibrosis, but worsened muscle and bone parameters. Specifically, KD exacerbated muscle wasting and atrophy-related gene expression, while in bone it impaired microarchitecture, increased resorption, and reduced mineralization. In vitro experiments on myotubes further clarified these effects: palmitate promoted atrophy and oxidative stress, whereas low doses of butyrate were protective, though high doses lost effectiveness. Overall, our findings highlight that while KD can improve glucose metabolism, liver function, and promote weight loss, it may also have detrimental effects on muscle and bone. Future studies should optimize timing, duration, and composition of ketogenic regimens to maximize benefits while minimizing risks.