Inhibition of serotonin-Htr2b signaling in skeletal muscle mitigates obesity-induced insulin resistance.

ABSTRACT: Obesity-induced insulin resistance is a major cause of metabolic disorders, including type 2 diabetes mellitus. Although peripheral serotonin (5-hydroxytryptamine, 5-HT) has been implicated in energy balance and metabolism, its effect on skeletal muscle insulin sensitivity remains unclear. Here we identified the 5-HT receptor 2b (Htr2b) as a critical regulator of insulin sensitivity and energy metabolism in the skeletal muscle. Using genetic and pharmacological approaches, we showed that muscle-specific Tph1-knockout (Tph1 MKO) mice fed a high-fat diet exhibited reduced body weight, increased lean mass and improved glucose tolerance compared with wild-type mice. The pharmacological inhibition of Htr2b in myotubes reversed palmitate-induced insulin resistance and increased glycolytic activi

SUBMITTER: Park S 

PROVIDER: S-EPMC12227683 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature