response to leptin

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a leptin stimulus. 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. It plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism]. [GOC:yaf]

Leptin, a hormone produced primarily by adipose tissue, plays a crucial role in regulating energy homeostasis, appetite, and metabolism. Its primary target is the hypothalamus, a brain region responsible for controlling these functions.

Upon binding to its receptor (LepR), leptin triggers a complex signaling cascade within the hypothalamus, leading to a reduction in appetite and an increase in energy expenditure.

**Here's a detailed breakdown of the process:**

1. **Leptin Binding:** Leptin binds to its receptor, LepR, located on neurons within the hypothalamus. This binding activates the JAK-STAT signaling pathway.

2. **JAK-STAT Pathway Activation:** The binding of leptin to LepR activates the Janus kinase (JAK) associated with the receptor. Activated JAK phosphorylates the receptor, creating a docking site for STAT proteins. STAT proteins bind to the phosphorylated receptor and are subsequently phosphorylated by JAK.

3. **STAT Dimerization and Nuclear Translocation:** Phosphorylated STAT proteins dimerize and translocate to the nucleus.

4. **Gene Transcription Regulation:** In the nucleus, STAT dimers bind to specific DNA sequences called STAT-binding elements (SBE), located within the regulatory regions of target genes. This binding leads to the transcription of these genes, resulting in the synthesis of proteins that regulate appetite and metabolism.

5. **Downstream Effects:** The downstream effects of leptin signaling are mediated by various neuropeptides and neurotransmitters, including:
* **POMC neurons:** Leptin activates POMC neurons, leading to the production of α-melanocyte-stimulating hormone (α-MSH). α-MSH acts as a potent anorexigenic signal, reducing appetite and promoting energy expenditure.
* **NPY neurons:** Leptin inhibits NPY neurons, reducing the release of neuropeptide Y (NPY), a potent orexigenic signal that stimulates appetite.
* **AgRP neurons:** Leptin also inhibits AgRP neurons, reducing the release of agouti-related peptide (AgRP), another orexigenic peptide.

**Overall, leptin signaling through the JAK-STAT pathway leads to a decrease in appetite and an increase in energy expenditure, ultimately contributing to weight regulation.**

**Note:** Leptin resistance, a condition where the body fails to respond adequately to leptin, can lead to obesity and other metabolic disorders.'
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Proteins (4)

Compounds (133)