In rodents fed high-fat diets, gut microbes boost hunger, trigger obesity

(credit: Joanna Servaes)

After several hints that gut microbes may be key players in the obesity epidemic, a new study provides a mechanistic explanation of how the intestinal inhabitants directly induce hunger, insulin resistance, and ultimately obesity in rodents.

After mice and rats were fed a high-fat diet, their gut microbes produced more acetate, a short-chain fatty acid made during bacterial fermentation. That acetate spread throughout the rodents’ bodies and into their brains where it activated the parasympathetic nervous system. This system, largely involving the vagus nerve, controls the body’s unconscious actions, such as digestion, excretion, and sexual arousal. By activating the parasympathetic nervous system, the microbe-made acetate spurred the rodents to produce more insulin, a hormone made by pancreatic β-cells that promotes calorie storage, as well as ghrelin, a hormone involved in hunger. The result was rodents that ate more developed insulin resistance—a precursor to diabetes—and became obese, the researchers report in Nature.

“This generates a positive feedback loop,” the authors conclude—which makes sense for foraging animals, they add. If a foraging animal stumbles upon a calorie-dense food in the wild, it would be advantageous if their gut signaled their brain to keep eating and store some energy, stocking up to survive leaner times. “However, in the setting of chronic exposure to calorically dense, abundant food, this gut microbiota–brain–β-cell axis promotes obesity and its related sequelae of hyperlipidaemia [high levels of lipids in the blood], fatty liver disease and insulin resistance,” the authors write.

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