Liver enzyme implicated in obesity

Obesity is due to a mismatch between the number of calories consumed and the amount of physical activity undertaken. In the brain, a region called the hypothalamus controls our eating behavior through its metabolism of fat molecules called fatty acids. Interestingly, eating too much in the short-term can result in a severe drop in the ability of the body to be satisfied by fat and to control blood sugar levels.

The researchers from Albert Einstein College of Medicine in New York have discovered that the enzyme called carnitine palmitoyltransferase-1 (CPT1A) may be implicated in this process.

In the study normal rats were placed on a lard-based diet to stimulate them to voluntarily overeat and gain weight. The researchers then inhibited CPT1A by delivering special molecules called “ribozymes” into the brain of the rats, to find that the animals ate dramatically less.

The treatment also improved the blood sugar levels of these animals, who suffered from a common metabolic impairment known as insulin resistance, in which the body is unable to respond properly to insulin. The authors report that this animal model of diet-induced obesity and insulin resistance displayed defective adaptation to an increase in fat availability coupled with a severe impairment in the ability of the brain to sense fat intake.

Further studies will be required to establish the critical role of this biochemical pathway in nutrient sensing in other animal models and, critically, in humans. The study will be appearing in the April issue of the Journal of Clinical Investigation.