SAT128 Low Concentration Of Butyrate Reverts PA-induced Atrophic Condition On C2C12 Myotubes

Disclosure: S. Tini: None. A. Antonioli: None. S. Reano: None. T. Raiteri: None. A. Scircoli: None. V. Antoniotti: None. I. Zaggia: None. N. Filigheddu: None. F. Prodam: None. Sarcobesity is a well-defined medical condition characterized by the coexistence between skeletal muscle atrophy and increased fat mass representing, nowadays, a relevant public health issue among the world population. Sarcobesity is often associated with the development of metabolic syndrome (MetS), insulin-resistance (IR), dyslipidaemia, and other pathologies such as cardiovascular diseases (CVDs) and type 2 diabetes (T2DM). The global increment of this condition has been favoured by changes in lifestyle and dietary habits as largely demonstrated. Particularly, Western Diet (WD), rich in saturated fats and sugars and poor in fibers, vitamins, and minerals seems to be the main cause of sarcobesity in association with low levels of physical activity. In recent years, Ketogenic Diet (KD) has been proposed as a fighting obesity therapy and as a new possible therapeutic strategy to counteract the WD detrimental effects on different tissues, i.e skeletal muscle that plays a key role in whole-body metabolism, glucose homeostasis and lipid use. KD regimen consists in a very low carbohydrates intake, high fat and adequate protein contents that cause the so-called “nutritional ketosis” with the production of Ketone bodies (KBs). KBs, such as beta-hydroxybutyrate (BHB), acetoacetate and acetone are the final products of the partial beta-oxidation of free fatty acid. They are short chain fatty acid produced in liver with different role on metabolism and they are used as a source of energy instead of glucose by different tissues including skeletal muscle. Preliminary experiments in our laboratory demonstrated that palmitate (PA), which is a saturated fat highly present in WD regimen, induces myotubes atrophy in dose dependent manner (100, 250, 500uM). The aim of the present study is to investigate not only if KBs have a direct effect on C2C12 skeletal muscle cells, but also if they are able to contrast the PA-induced atrophy in myotubes. We demonstrated with a co-treatment that sodium butyrate (s-BU), which is the main KB produced during ketogenesis, is able to prevent PA negative effects in skeletal muscle cells when it is used at low concentration. In contrast, high doses of BU reduced C2C12 diameters suggesting that KBs could have opposite effects depending on their concentration. Currently, other short chain fatty acids and KBs, i.e pyruvate and acetoacetate are under investigation in our laboratory. Collectively, these data suggest that KD could represent a promising intervention to contrast WD damages on skeletal muscle in overweight/obese individuals. Presentation: Saturday, June 17, 2023