Obesity Linked To Gut-Brain Connection

A high fat diet (HFD) and lack of physical activity can cause obesity and lead to various diseases such as cancer, diabetes, and heart disease. Obesity is a medical condition which causes excess body fat to accumulate and is one of the leading causes of preventable death worldwide. Although the most effective obesity treatment is surgery, other effective and less invasive treatments and therapeutics are needed. We have previously reported on Fighting Fat With Fat, Rap1: Potential Target To Combat Obesity and New Gene Target to Prevent Obesity. Leptin is the satiety hormone produced by fatty tissue that inhibits appetite. People suffering from obesity do not respond to leptin and thus eat excessively. Researchers are now exploring the gut-brain connection that may help determine why eating a HFD leads to overeating, weight gain, and obesity.

In a recent study, researchers examined the links between leptin and the gastric inhibitory polypeptide (GIP). This hormone is produced in the gut to stimulate insulin secretion. Previous studies have also shown GIP is involved in controlling energy balance under conditions of nutrient excess. Mice fed a HFD produce increased amounts of GIP in the gut that inhibited leptin signaling in the brain. This suggests the satiety signal is switched so the mice continued to eat and gain weight. GIP increased the active form of the small GTPase Rap1 in the brain. Furthermore, blocking GIP receptors then restored leptin responses in HFD fed obese mice, that caused the animals to start to eat less and led to weight loss. Further studies are needed to develop weight-loss strategies that can restore the brain’s ability to respond to leptin.

For more information: https://www.jci.org/articles/view/126107

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