In high-fat diet-fed rats, the combination of dapagliflozin and 16:8 intermittent fasting restores serum acetate and propionate levels to normal and reduces adipose GPR43 receptor expression by 56.1% compared to high-fat diet controls, indicating enhanced gut microbiota signaling that increases satiety hormone production and decreases appetite.

When rats eat a high-fat diet, gut bacteria produce fewer short-chain fatty acids like acetate and propionate, which causes fat cells to make too much of a receptor called GPR43. This overactive receptor suppresses appetite-controlling hormones. When the rats are given a drug that increases sugar loss in urine and fast for 16 hours each day, their gut bacteria recover and start making normal levels of acetate and propionate again. These fatty acids bind to GPR43 receptors until they are fully occupied, causing the body to reduce the number of these receptors. With fewer receptors and more fatty acids present, the gut releases more satiety hormones that signal the brain to stop eating. The brain responds by activating neurons that reduce hunger and food intake.