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What Is Leptin Resistance?

By Tracey Roizman, D.C.

Leptin, a hormone produced by fat tissue, serves a negative feedback role for management of weight, appetite and other metabolic parameters. Leptin exerts its effects on the hypothalamus, where the brain's appetite control centers are located. Leptin resistance can occur when too much circulating leptin affects the brain's sensitivity to leptin. The resulting condition leads to a lack of leptin's appetite-regulating effect and is known as leptin resistance. Research has revealed some illuminating information on the process of leptin resistance.


Leptin resistance may be linked to chronic inflammation, according to a study published in February 2011 in the "American Journal of Physiology, Endocrinology and Metabolism." In the study, leptin supplementation decreased food intake in a group of control animals and exposure to inflammatory molecules suppressed appetite in another group. However, leptin supplementation did not have the same effect on animals with chronic inflammation. The researchers concluded that leptin shares similar pathways to inflammation and chronic inflammation may lead to leptin resistance.

Individual Variability

Wide individual variation in leptin levels may cloud the issue of leptin's role as a feedback mechanism to control appetite and weight gain, according to a study published in the April 2001 issue of the "Proceedings of the National Academy of Sciences." Studies on both laboratory animals and humans show that leptin levels also increase with age due to increases in fat deposits. As a result, experiments that have attempted to use leptin therapy to treat obesity have been met with resistance from already high leptin levels, making leptin ineffective as a supplemental therapy for weight loss.

Similar to Insulin Resistance

Leptin resistance is extremely common in overweight and obese people and is similar to insulin resistance in diabetics, according to the website Leptin resistance occurs because leptin transport into the hypothalamus -- the area of the brain that controls appetite -- shuts down to prevent overload of leptin messages. The result is high circulating leptin levels, but no leptin reaching the brain where it can have a regulating effect on appetite. As a result, hunger messages prevail and lead to overeating and weight gain.

Eat Slowly

Eating more slowly may help prevent leptin resistance, according to Harvard University. There is evidence that leptin, in combination with chemical messengers released by the intestines when food is present, amplifies signals of fullness, encouraging you to stop eating. Leptin also affects the brain to produce the pleasurable feeling associated with fullness. Eating more slowly allows these signals time to kick in and do their job so you won't overeat, lessening the risk of developing leptin resistence.

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