Hormonal

Oral butyrate supplementation reduces appetite and prevents diet-induced obesity primarily by activating the gut-brain neural circuit (vagal nerve) to suppress orexigenic neurons and increase sympathetic outflow to brown adipose tissue.

Oral butyrate supplementation (specifically sodium butyrate mixed into a high-fat diet at 5% weight/weight in this study) reduces food intake and prevents obesity in mice. The key is that it must be taken orally to trigger the gut-brain-vagus nerve pathway; injecting it does not work. It works by suppressing hunger signals in the brain and activating brown fat to burn energy. For humans, this suggests that dietary sources of butyrate (like fiber fermentation) or oral supplements might help manage appetite and weight, but the exact effective dose and long-term safety in humans require further clinical validation.