Deficiency of neuronal LGR4 reduces obesity via hypothalamic leptin signaling

ABSTRACT: The metabolic effects of LGR4 remain largely unknown. Here, we showed that knockdown of Lgr4 in nestin progenitor or Sp1 mature neurons reduced HFD-induced obesity by increasing energy expenditure and inhibiting food intake. Deficiency of LGR4 in AgRP neurons increased energy expenditure, and inhibited food intake, leading to alterations in glucose and lipid metabolism. Knock-down of Lgr4 in Sf1 neurons enhanced energy expenditure, reduced adiposity, and improved glucose and lipid metabolism. The metabolic benefits of neuronal LGR4 occurred via improvement of leptin signaling in AgRP and Sf1 neurons. Knockdown of Lgr4 in nestin, Sp1, AgRP or Sf1 neurons decreased hypothalamic SOCS-3, and increased phosphorylation of STAT3. These alterations were associated with a significant reduction in t

SUBMITTER: Weizhen Zhang 

PROVIDER: S-SCDT-10_1038-S44319-025-00398-5 | biostudies-other |

REPOSITORIES: biostudies-other