Colonic Fermentation and Acetate Production in Youth with and without Obesity

Background: In the last few years, there has been a growing interest in the role of gut microbiota in the development of obesity and its complications. Objectives: In this study, we tested the following hypotheses: 1) lean youth and youth with obesity experience a different capability of their gut microbiota to ferment carbohydrates and produce acetate; and 2) colonic acetate may serve as a substrate for hepatic de novo lipogenesis (DNL). Methods: Nineteen lean youth [mean +/- SE BMI (in kg/m(2)): 21.8 +/- 0.521] and 19 youth with obesity (BMI: 35.7 +/- 1.66), ages 15-21 y, frequency-matched by age and sex, underwent a fasting 10-h sodium [d(3)]-acetate intravenous infusion to determine the rate of appearance of acetate (Ra-acet) into the peripheral circulation before and after an oral dose of 20 g of lactulose. Pre- and post-lactulose Raacet values were determined at a quasi-steady state and changes between groups were compared using a quantile regression model. Acetate-derived hepatic DNL was measured in 11 subjects (6 youth with obesity) and its association with Raacet was assessed using Spearman correlation. Results: Mean +/- SE Raacet was not different before lactulose ingestion between the 2 groups (7.69 +/- 1.02 mu mol . kg(-1) . min(-1) in lean youth and 7.40 +/- 1.73 mu mol . kg(-1) . min(-1) in youth with obesity, P = 0.343). The increase in mean +/- SE Raacet after lactulose ingestion was greater in lean youth than in youth with obesity (14.7 +/- 2.33 mu mol . kg(-1) . min(-1) and 9.29 +/- 1.44 mu mol . kg(-1) . min(-1), respectively, P = 0.001). DNL correlated with Raacet, calculated as changes from the pre- to the post-lactulose steady state (rho = 0.621; P = 0.046). Conclusions: These data suggest that youth with obesity ferment lactulose to a lesser degree than youth without obesity and that colonic acetate serves as a substrate for hepatic DNL.