Aims: It has been reported that there is a close relationship between sarcopenia obesity and metabolic disorder such as lipid metabolism. Here we investigated the effect on lipid metabolism of the sodium glucose cotransporter-2 inhibitor (SGLT-2i) luseogliflozin in skeletal muscle. We preformed microarray analysis of mRNA in skeletal muscle and investigated the lipid profile in skeletal muscle and serum.
Methods: Eight-week-old mice were fed a standard diet or a standard diet supplemented with luseogliflozin (0.01% w/w chow) for 8 weeks. Mice were divided into the following three genotype/diet groups: Db/m mice without (w/o) SGLT-2i, Db/Db w/o SGLT-2i, and Db/Db with SGLT-2i. After 8 weeks of diet, in each group, body weight, glucose tolerance, muscle weight and cross-sectional area, free fatty acid concentration, muscle and gene expression in serum were investigated.
Results: The ratio of soleus muscle to body weight and the cross-sectional area of soleus muscle were significantly higher in Db/Db mice with SGLT-2i than in Db/Db mice w/o SGLT-2i. In addition, the concentration of saturated fatty acids in skeletal muscle and serum of Db/Db mice with SGLT-2i was significantly lower than that w/o SGLT2i, and the expression of Fasn, Elovl6, and Scd1, which are involved in fatty acid synthesis, in skeletal muscle was significantly increased in Db/Db w/o SGLT-2i compared to Db/m mice with SGLT-2i, and significantly decreased in Db/Db with SGLT-2i compared to mice w/o SGLT-2i. Furthermore, in cell experiments using C2C12 myotube cells, the administration of saturated fatty acid increased the expression of muscle atrophy-related genes.
Conclusion: The administration of luseogliflozin suppressed skeletal muscle atrophy and reduced the concentration of saturated fatty acids in skeletal muscle. Based on these findings, we hypothesized that secondary effects, other than the hypoglycemic effects of SGLT2i, might lead to the alleviation of obesity-dependent sarcopenia.
R. Bamba: None. T. Okamura: None. Y. Hashimoto: None. T. Senmaru: None. M. Hamaguchi: Research Support; Spouse/Partner; AstraZeneca K. K. M. Fukui: None.