Leptin receptor

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Leptin receptor (LEPR) is a protein on cell surfaces that binds leptin, a hormone made by fat cells. When leptin attaches to LEPR, it sends signals inside the cell that help control hunger, energy use, and body fat.

What it does
- In the brain, especially the hypothalamus, LEPR helps regulate appetite and how the body uses energy.
- It works as a single-pass transmembrane receptor, meaning it sits in the cell membrane with a part outside the cell, a single membrane-spanning segment, and a part inside the cell.
- Leptin binding to LEPR starts a cascade of signals that influence feeding, energy balance, and fat storage.

Structure in simple terms
- The outside part of LEPR has several regions (CRH1, Ig-like, CRH2, and two FNIII domains).
- The CRH2 region is important for binding leptin, and the FNIII regions help turn the signal on. The CRH1 region may help regulate binding but isn’t essential for it.
- The receptor has three main regions: extracellular (outside the cell), transmembrane (through the membrane), and intracellular (inside the cell).

Where it’s found
- The LEPR gene is located on chromosome 1 in humans. It has similar forms in mice and other animals.
- Leptin receptors are present in many tissues, including the brain and placenta during pregnancy, and they play roles in development.

How scientists learned about it
- LEPR is a member of the cytokine receptor family. It was identified in the mid-1990s after researchers connected leptin signaling with the receptor.
- The receptor’s interaction with leptin has been studied using structures of the extracellular domain, showing how two leptin molecules can bind with two receptors to form a signaling complex.

Why it matters
- Proper LEPR function helps keep body weight and energy use in balance. Problems with LEPR signaling can contribute to obesity and may affect susceptibility to certain infections.
- The db/db mouse model, which has a broken leptin receptor, becomes obese and develops related metabolic problems, providing a useful system to study obesity and diabetes.
- Leptin and its receptor also have roles in pregnancy, helping support fetal development through placental signaling.

In short, the leptin receptor is the gateway through which the body’s fat-derived leptin hormone controls hunger, energy use, and weight, with important roles in development and health.