Continuous caloric restriction and intermittent fasting ameliorate the disrupted postprandial response of short-chain fatty acids in obese mice. Continuous caloric restriction and intermittent fasting ameliorate the disrupted postprandial response of short-chain fatty acids in obese mice

Caloric restriction (CR) and intermittent fasting (IF) are both promising approaches for treating obesity and its complications. However, long-term adherence to CR can be challenging, and it is unclear how CR and IF compare in terms of their effectiveness. Additionally, the molecular mechanisms underlying the metabolic improvements of IF are uncertain, and its efficacy in treating established obesity is poorly understood. We examined two different IF regimens in diet-induced obese mice on a hypercaloric diet or subjected to CR and compared them with continuous CR. We assessed metabolic parameters, gut microbiota composition, and fasting and postprandial short-chain fatty acids (SCFAs) levels. We found that IF with a hypercaloric diet effectively mitigated weight gain and improved metabolic health to an extent comparable with continuous CR. Notably, the IF regimens did not significantly modify gut microbiota composition but increased the levels of fecal SCFAs, particularly in the postprandial period, mirroring the effects of CR. Combining IF with CR yielded the most substantial improvement in glucose tolerance and exerted a more pronounced effect on gut microbiota composition, albeit with a lesser impact on SCFAs. Importantly, we identified Alistipes finegoldii as a potential SCFAs producer associated with improved metabolic outcomes. In conclusion, IF on a hypercaloric diet protects against obesity, primarily through the modulation of gut microbiota metabolites. Conversely, IF with CR improves glucose metabolism by influencing gut microbiota composition. Our findings underscore the potential for interventions to restore the postprandial response of SCFAs in obesity, even in the absence of weight loss.