1137-P: Anti–Skeletal Muscle Atrophy Effect of Luseogliflozin via Lipidome Modification in db/db Mice

It has been controversial that the sodium glucose cotransporter-2 inhibitor (SGLT2i) have a protective effect for muscle atrophy. We previously reported that muscle atrophy in Db/Db mice were improved by luseogliflozin via upregulation of foxo1 expression. Here we show that systemic or local lipidome were altered in Db/Db mice, which were modified by luseogliflozin. Additionally, we investigated the underling molecular mechanisms between altered lipidome and gene expressions in the atrophic soleus muscle. Eight-week-old mice were fed a standard diet or the standard diet with added luseogliflozin (0.01% w/w in chow) for 8 weeks. The mice were divided into the following three genotype/dietary groups: Db/m mice without (w/o) SGLT2i, Db/Db w/o SGLT2i, and Db/Db with SGLT2i. Concentration of stearate acids in blood in Db/Db mice with SGLT2i decreased compared to that without. The expression of scd1 or foxo1 increased in Db/Db mice w/o SGLT2i and decreased in Db/Db mice with SGLT2i. Stearate acids in blood increased in Db/Db mice, which increased stearate acids in skeletal muscle. Increased stearate acid concentration in skeletal muscle stimulates the expression of scd1, on the other hand, the administration of luseogliflozin decreased stearate acids in blood and skeletal muscle, which decreased the expression of scd1 in skeletal muscle.