The effects of serotonin by Tph1 on skeletal muscle

Reducing circulating serotonin by inhibition of Tph1 increases the sensitivity of BAT cells and this drives thermogenesis by fat and glucose oxidation. Here we report Insulin sensitivity changes by regulating Serotonin on skeletal muscle. Improved glucose tolerance and insulin sensitivity in HFD Tph1 KO mice. Inhibiting Tph1 increases AMPK activity, glucose uptake, myofiber size and decreases lipid droplet accumulation in HFD mice skeletal muscle. Inhibiting Tph1 in muscle showed activation of SIRT1/LKB1/AMPK pathway in skeletal muscle cells and increased p-ACC. Theses results indicates that protected insulin resistance and myosteatosis on skeletal muscle by lack of Serotonin by Tph1 on skeletal muscle. Overall design: Non-pathogenic mouse strains on a C57BL/6 background; expressing cre recombinase under the Mlc(Myosin Light Chain) promoter in which the exon 4,5 of the Tph1 gene is floxed.