A multi-institutional team of researchers led by Dr. Makoto Fukuda, from Baylor College of Medicine, found that mice on a high-fat diet show increased levels of gastric inhibitory polypeptide (GIP), a hormone produced in the gut that is involved in managing the body’s energy balance, according to apress release. Excess GIP travels through the blood to the brain, where it inhibits the action of leptin, the satiety hormone—and then the mice continued eating, and gained weight.
“My colleagues and I started looking for what causes leptin resistance in the brain when we eat fatty foods,” Dr. Fukuda said in the release. “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.”
Further experiments revealed that, when GIP is prevented from interacting with its receptor, obese mice on a high-fat diet lost weight—but lean mice fed a normal diet showed no weight alteration.
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“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,” Dr. Fukuda said. “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. Blocking the interaction of GIP with the hypothalamus of obese mice restores leptin’s ability to inhibit appetite and reduces body weight.”The release notes that, while more research is needed, the researchers hope that these findings might one day translate to weight loss strategies that block GIP and restore the brain’s ability to respond to leptin.
