Gut-brain Connection Explains How Overeating Causes Weight Gain

Newly discovered gut-brain connection helps scientists unravel how those extra servings of our favorite foods lead to weight gain and obesity. The study led by scientists at the Baylor College of Medicine involved teams from several other institutions as well. We know that overeating results in weight gain and obesity, but the reasons for that remain unclear. The study team hoped to determine the precise mechanism by which overeating causes obesity and whether their observations could help evolve potential weight-loss strategies in the future.

The findings of the study appear in the Journal of Clinical Investigation.

Decoding How Overeating Leads To Obesity

• Gastric Inhibitory Peptide (GIP) is a hormone formed in the gut when we eat and is involved in regulating energy balance. When we eat foods rich in fat, levels of GIP in the gut are elevated
• Leptin is another hormone formed in the brain and creates a feeling of satiety when our stomach is full and prevents overeating
• The study team wanted to find out if GIP could be playing a role in blocking leptin resulting in weight gain. The study was carried out in mice
• The study team confirmed possible GIP leptin connection by finding that GIP receptor, which binds to GIP and mediates its activity was indeed present in the brain
• Next, the scientists analyzed the effects of blocking the GIP receptor by infusing a monoclonal antibody directly into the brain, effectively preventing binding of GIP with GIP receptor.
• The team observed that in obese mice fed on a high-fat diet, there was marked weight loss with reduction of body fat and blood glucose levels.
• On the other hand, normal chow-fed lean mice infused with the monoclonal antibody neither showed a reduction in dietary intake nor did they lose weight, suggesting that GIP-leptin effects are specific to obesity caused by diet
• Also genetic modification of the mice, making them deficient in leptin demonstrated that infusion of the specific monoclonal antibody did not cause reduction of appetite or weight loss, suggesting that GIP effects in the brain were mediated through leptin hormone

The findings of the study suggest that interaction of GIP and its receptor in the hypothalamus, (a part of the brain that mediates hunger and satiety) could be critical in causing leptin resistance and weight gain, especially when consuming high fat diet.

Dr. Makoto Fukuda, assistant professor of pediatrics at Baylor and Texas Children's Hospital, and corresponding author of the study, said: "We didn't know how a high-fat diet or overeating leads to leptin resistance. 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."

Scope of the Study

The findings of the study pave the way for future research to evolve weight loss strategies by blocking the effects of the gastric inhibitory peptide (GIP), and allowing the normal activity of leptin, the satiety hormone

In summary, eating a healthy and well-balanced diet, and avoiding fatty foods ensures that GIP levels are not elevated and leptin hormone normally works, producing a feeling of satiety and preventing overeating and weight gain.

Reference:

1. Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition - (https://www.jci.org/articles/view/126107)

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Source-Medindia