Respuestas metabólicas al ayuno y la realimentación de 48 horas en adultos con y sin obesidad

Metabolic flexibility - the ability to adapt substrate utilization to availability - is commonly impaired in individuals with obesity. While short-term fasting promotes lipid utilization, it may lead to subsequent metabolic inflexibility by blunting carbohydrate metabolism upon refeeding. However, the extent to which this differs in obesity remains unknown.

To examine if a 48-hour fast differentially affects substrate utilization during refeeding in individuals with and without obesity.

Adults classified as lean (n = 16) or with obesity (n = 16) (8 males and 8 females per group) completed a 48-hour fast followed by a mixed meal tolerance test (MMTT). Respiratory exchange ratio (RER), glucose, β-hydroxybutyrate (BHB), insulin, and free fatty acid (FFA) levels were measured at baseline, after 48-hours of fasting, and 1 and 2 hours postprandially to assess substrate utilization.

Individuals with obesity exhibited baseline hyperinsulinemia despite similar glucose levels when compared to lean individuals. Fasting reduced circulating insulin and glucose, and elicited a shift toward fat oxidation in both groups, reflected by decreased RER and elevated FFAs (P < 0.001). Despite similar FFA concentrations, individuals with obesity demonstrated lower BHB concentrations (P < 0.001) following the fast when compared to their lean counterparts. Upon refeeding, individuals with obesity demonstrated lower 2-hour postprandial glucose excursions compared to lean participants (P < 0.001).

The presence of obesity may elicit a paradoxical advantage in restoring carbohydrate metabolism following short-term fasting. We speculate that fasting may alleviate basal hyperinsulinemia-induced insulin resistance, which partially counteracts fasting-induced glucose intolerance.

This trial was registered on ClinicalTrials.gov (NCT05886738).