Leptin Resistance and Obesity

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

Leptin plays an important role in regulating appetite and body weight. Leptin binds to a form of leptin receptor present in the cells of the hypothalamus. This stimulates an intracellular signalling pathway that leads to down-regulation of the expression of receptors involved in increasing appetite.

Abnormalities in the production of leptin are associated with alterations in body weight.

Leptin resistance in obesity

Leptin interacts with specific leptin receptors to inhibit excess feeding and its elevation and obesity is therefore often thought to indicate a leptin resistant state. Leptin resistance in obese individuals is thought to arise due to a blunted response of leptin to caloric intake.

When leptin levels are persistently high due to over eating, there may be down regulation of the leptin receptor and therefore reduced sensitivity to the hormone. In addition, the absence of leptin or the leptin receptor leads to uncontrolled eating, therefore increasing the risk of obesity.

Leptin resistance mechanism

There are several important genetic and environmental factors that can regulate and influence leptin production and sensitivity to the hormone. Some possible underlying mechanisms of leptin resistance include:

• Abnormal cellular signal transduction pathways after leptin binds to its receptors
• Interactions between higher cortical centers that regulate motivation and the nerve networks of feeding behavior
• Genetic mutations of the leptin gene that codes for the leptin hormone

Further Reading

• All Leptin Content
• What Does Leptin Do?
• What is Leptin?
• Leptin Mechanism
• Leptin Mutations