Results may be useful for developing a new type of weight-loss medicine.

The hormone leptin is responsible for signaling to the brain (in the hypothalamus) the amount of fat stored in the body. When there is a high amount of stored fat, leptin levels are high, and vice versa. High levels are supposed to indicate that less food and more exercise are needed. But for many, this negative feedback loop is broken. The brain does not receive the correct signal, a condition referred to as leptin resistance.

Leptin resistance is believed to be due to a variety of factors, including inflammatory signaling in the hypothalamus, elevated free fatty acids in the bloodstream and also elevated levels of leptin. Losing weight for people with leptin resistance is challenging because as fat is lost, the leptin levels drop and leptin signaling may begin working correctly, leading to feelings of hunger and a desire to conserve energy. 

Research at the University of California, San Diego (UCSD) recently published a paper in Science Translational Medicine regarding new findings about leptin resistance. Mice fed a high-diet produced matrix metalloproteinase-2 (MMP-2), which clips leptin hormone receptors on the surfaces of neuronal cells in the hypothalamus. Without these receptors, the leptin cannot bind to the neuronal cells and the brain does not detect the leptin.

Lead author Rafi Mazor of UCSD, believes this discovery provides access to a new field of study for metabolic disease. The research team, which also includes scientists at the Salk Institute for Biological Studies in La Jolla, Tel Aviv University in Israel, and Monash University in Australia, hopes a large-scale clinical trial will be conducted to investigate the potential for MMP-2 inhibitors to serve as weight loss drugs.