Project description: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.
Project description:It is known that reducing circulating serotonin by inhibiting Tph1 increases the sensitivity of BAT cells and this drives thermogenesis by fat and glucose oxidation. In our results inhibiting Tph1 in muscle showed activation of SIRT1/LKB1/AMPK pathway in skeletal muscle cells and increased p-ACC. Also, it's known that inhibiting adipose Htr2b signaling ameliorates HFD-induced systemic insulin resistance. Here we report insulin sensitivity changes by regulating serotonin in skeletal muscle by Htr2b. Inhibiting Htr2b increases AMPK activity, glucose uptake, and myofiber size and decreases lipid droplet accumulation in HFD mice skeletal muscle. These results indicate improved insulin resistance and myosteatosis in skeletal muscle by lack of Serotonin by Tph1/Htr2b on skeletal muscle.
Project description:Serotonin in the mammary gland is known to regulate processes such as calcium homeostasis, tight junction permeability, and milk protein gene expression. The objective of this study was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate-limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 knock-out mice dams (serotonin deficient) and compared them to wild-type dams and also Tph1 deficient dams injected daily with 5-HTP. Mammary gland tissues were collected on day 10 of lactation and then analyzed by RNA sequencing. Genome-wide gene expression profiles of 12 mouse mammary gland samples were evaluated using RNA sequencing; these 12 samples belong to wild-type dams (WT; n = 4), Tryptophan hydroxylase (Tph1) knock-out dams (KO; Tph1 deficient; n = 4), and Tph1 deficient dams injected daily with 5-HTP (RC; n = 4). Mammary tissues were collected on day 10 of lactation and then underwent RNA extraction, library generation, and subsequent sequencing.