Gut-brain connection details the role of overeating in the onset of obesity

New findings published by researchers at Baylor College of Medicine give fresh insight into how a gut-brain connection helps us better understand why eating extra servings translates into weight gain. The results appeared in the Journal of Clinical Investigation.

“We have uncovered a new piece of the complex puzzle of how the body manages energy balance and affects weight,” said Dr. Makoto Fukuda, co-author of the study.

In the study, higher levels of the hormone, known as gastric inhibitory polypeptide (GIP), was observed in rodents with high-fat food intake. The findings detail that during increased levels of GIP, which inhibits the action of leptin – a hormone associated with appetite and the regulation of metabolism – rodents still overeat and subsequently gain weight. By inhibiting GIP’s interaction with the brain of rodents, increased levels of leptin could block appetite and lead to weight loss, researchers say.

According to previous findings, leptin plays a major role in the control of body weight, by bringing forth the sensation of feeling full after enough food intake. This, however, does not occur in obesity caused by a high-fat diet, where leptin signals do not affect the body, resulting in further food intake and weight gain.

“My colleagues and I started looking for what causes leptin resistance in the brain when we eat fatty foods. Using cultured brain slices in petri dishes we screened blood circulating factors for their ability to stop leptin actions. After several years of efforts, we discovered a connection between the gut hormone GIP and leptin,” Fukuda explained.

Researchers first set out to find out if the GIP receptor is expressed in the brain, then, by infusing a monoclonal antibody in the brain, they examined the outcome of GIP receptor inhibition on obesity.

“The animals ate less and also reduced their fat mass and blood glucose levels. In contrast, normal chow-fed lean mice treated with the monoclonal antibody that blocks GIP-GIP receptor interaction neither reduced their food intake nor lost body weight or fat mass, indicating that the effects are specific to diet-induced obesity,” said Fukuda.

“In summary, when eating a balanced diet, GIP levels do not increase and leptin works as expected, triggering in the brain the feeling of being full when the animal has eaten enough and the mice stop eating. But, when the animals eat a high-fat diet and become obese, the levels of blood GIP increase. GIP flows into the hypothalamus where it inhibits leptin’s action. Consequently, the animals do not feel full, overeat and gain weight. Blocking the interaction of GIP with the hypothalamus of obese mice restores leptin’s ability to inhibit appetite and reduces body weight.”