A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies.

ABSTRACT: The hormone leptin, primarily secreted by adipocytes, plays a crucial role in regulating whole-body energy homeostasis. Homozygous loss-of-function mutations in the leptin gene (LEP) cause hyperphagia and severe obesity, primarily through alterations in leptin's affinity for its receptor or changes in serum leptin concentrations. Although serum concentrations are influenced by various factors (e.g., gene expression, protein synthesis, stability in the serum), proper delivery of leptin from its site of synthesis in the endoplasmic reticulum via the secretory pathway to the extracellular serum is a critical step. However, the regulatory mechanisms and specific machinery involved in this trafficking route, particularly in the context of human LEP mutations, remain largely unexplored. We have

SUBMITTER: Baird HJM 

PROVIDER: S-EPMC11366920 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature