leptin-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by leptin binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Leptin is a hormone manufactured primarily in the adipocytes of white adipose tissue, and the level of circulating leptin is directly proportional to the total amount of fat in the body. [GOC:mah, GOC:signaling, GOC:yaf]

Leptin, a hormone primarily produced by adipocytes, plays a crucial role in regulating energy homeostasis and metabolism. Its signaling pathway, initiated by binding to the leptin receptor (LepR), a transmembrane protein expressed in various tissues, is a complex cascade of events that ultimately influences appetite, energy expenditure, and overall metabolic balance.

Upon leptin binding, LepR undergoes dimerization and autophosphorylation, triggering the activation of downstream signaling molecules. Janus kinase 2 (JAK2) is recruited to the cytoplasmic domain of LepR, leading to its phosphorylation and subsequent activation. Activated JAK2 then phosphorylates signal transducer and activator of transcription 3 (STAT3) on tyrosine residues, enabling its dimerization and translocation to the nucleus.

In the nucleus, STAT3 dimers bind to specific DNA sequences, leading to the transcription of target genes involved in energy metabolism, appetite regulation, and immune function. These genes include genes encoding proteins that suppress appetite, such as pro-opiomelanocortin (POMC), and genes encoding proteins that stimulate energy expenditure, such as uncoupling protein 1 (UCP1).

Additionally, leptin signaling also activates other downstream pathways, including the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, the mitogen-activated protein kinase (MAPK) pathway, and the suppressor of cytokine signaling (SOCS) pathway. These pathways contribute to the diverse effects of leptin on metabolism, inflammation, and immune responses.

Leptin resistance, a condition characterized by reduced sensitivity to leptin's actions, is a common feature of obesity and metabolic disorders. This resistance can arise from various factors, including impaired leptin signaling, altered LepR expression, and increased levels of inflammatory cytokines.

Understanding the intricate mechanisms of leptin-mediated signaling is crucial for developing effective strategies to combat obesity, diabetes, and other metabolic diseases. Research efforts are continuously being made to develop novel therapeutic approaches that target the leptin pathway and restore normal metabolic function.'
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Proteins (4)

Compounds (68)