What Are the Side Effects of Leptin?

Leptin is a hormone made and secreted by fat-storing cells. It regulates energy usage and expenditure, glucose and fat metabolism, and neuroendocrine and immune function. Leptin decreases fat production and hunger and many thought that it would be effective in treating obesity. However, obesity is accompanied by leptin resistance, meaning leptin does not work well in the body. A clinical trial study published in “Diabetes, Obesity and Metabolism” found that leptin treatment does not significantly reduce weight in obese individuals.

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Because leptin is a hormone with profound effects on energy homeostasis, metabolism and immune and neuroendocrine function both a deficiency of leptin and an excess of leptin results in the dysfunction of multiple organs. More research in humans needs to be conducted in order to determine whether acute or chronic administration of leptin causes serious side effects.

Sympathetic Nervous System

Leptin stimulates the sympathetic nervous system, also known as the “flight-or-fight” response. This part of the nervous system regulates many body responses including heart rate, gut motility, blood vessel constriction, bone formation, sweating and blood pressure. Reported in the January 2010 issue of “Current Opinion in Nephrology and Hypertension” high levels of leptin in obese individuals may play a role in the development of hypertension and other cardiovascular abnormalities 1.


A review article published in a 2009 issue of “Endocrine Regulations” stated that leptin increases molecules that induce inflammation in animals and may contribute to the development and progression of autoimmune responses. This study also reported there is some evidence to suggest that leptin plays a role in the development of rheumatoid arthritis in humans, however the studies are controversial. A clinical trial study published in “Diabetes, Obesity, and Metabolism” reported the only adverse effect of leptin administration in overweight individuals was injection site reactions. A review of leptin in the “American Journal of Clinical Nutrition” reported that leptin replacement therapy improved immune function in children with congenital leptin deficiency. Also, many animal studies demonstrate that leptin positively modulates the immune system and is protective against infectious disease.

Breast Cancer

Obesity, a disorder in which leptin levels are high, is a risk factor for breast cancer. A study reported in the 2010 issue of “Endocrine-related Cancer” that leptin increases the growth of mammary cells in the laboratory and that the leptin receptor was elevated in humans with breast cancer 3. While there is some evidence to suggest that high circulating leptin levels in the body may contribute to breast cancer progression, no studies have been conducted to demonstrate that leptin treatment causes breast cancer.

Blood Glucose

It was reported in a study in the “Proceedings of the National Academy of Sciences” that leptin potentiates the effects of insulin 4. If this is the case, injected leptin could potentially increase the frequency or severity of hypoglycemia in diabetic patients who are also taking insulin or oral anti-diabetic drugs.