Endocrine Abstracts

JOINT2782

The Western diet (WD), marked by elevated levels of sugars and saturated fats, significantly contributes to obesity and its related health complications. Its influence on insulin resistance and inflammation has been associated with several conditions, such as type 2 diabetes mellitus (T2DM), metabolic-associated steatotic liver disease (MASLD), and metabolic syndromes (MetS). Ketogenic diets (KDs) represent dietary approaches characterized by minimal carbohydrate intake, high fat, and adequate protein levels. Energy is sourced from ketone bodies (KBs), derived from fat oxidation and protein metabolism. Given the increasing evidence supporting the effectiveness of KDs in reducing inflammation, oxidative stress, and improving mitochondrial function, we hypothesized that KDs could hold promise in addressing obesity-related conditions, including sarcobesity. To test this hypothesis, we subjected mice to a Western diet (WD) for 16 weeks, followed by a transition to an ad libitum KD, or continued adherence to WD for an additional 4 or 8 weeks. Our finding demonstrated that within the muscle, a period in KD after WD is sufficient to influence the expression of genes associated with atrophy, autophagy and mitophagy. By exploring mechanisms implicated in muscle loss, we observed that KD leads to a significant reduction in branched-chain amino acids (BCAAs), whose levels are notably elevated in mice fed with WD, that apart their association with inflammation, could be used as primary source to produce ketone bodies in the liver. Finally, to further investigate the impact of fatty acids and KBs on muscle cells, we mimic in vitro WD and KD examining various doses of palmitate (PA) and butyrate (BU) on C2C12-derived myotubes. PA significantly reduced myotube diameter in a dose-dependent manner but also induces ROS production, and mitochondrial membrane depolarization. In contrast, low doses of BU protected against PA-induced atrophy in myotubes, while high doses appear to be ineffective or may even contribute to atrophy. Our findings suggest that KD could be detrimental on the muscle. Studies on tailored doses of ketone bodies are needed to understand if they really improve muscle performances.