Abstract

Introduction: Bile acids (BAs) are synthesized in the liver from cholesterol, and gut microbiota transform the host-derived primary BAs into secondary BAs in the intestine. Emerging evidence suggests that different types of circulating BAs may play pivotal roles in regulating energy metabolism and body adiposity. Hypothesis: We comprehensively examined whether changes in different BA subtypes after consuming weight-loss diets were associated with improvements in energy metabolism and body adiposity among patients with obesity. Methods: This study included 551 overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of 14 types of BAs (primary and secondary unconjugated BAs and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention; changes in BAs from baseline to 6 months after the intervention were calculated. We evaluated changes in resting energy expenditure, weight, and waist circumference. Also, body composition was assessed by the dual-energy X-ray absorptiometry (DEXA) scans, and fat distribution was assessed by computed tomography (CT) scans. Results: At baseline, higher primary and secondary BAs were related to greater degrees of adiposity and energy expenditure. At 6 months after the intervention, greater decreases in primary BAs (cholic acid [CA] and chenodeoxycholic acid) and secondary BAs (deoxycholic acid [DCA] and lithocholic acid [LCA]) and their conjugated subtypes (except for glycolithocholic acid) were significantly associated with more decreases in weight and waist circumference at 6 months after the intervention (P values after controlling for the multiple testing, P FDR <0.05). Greater reductions in the primary BAs (both unconjugated and conjugated types) and secondary BAs (DCA and its taurine-/glycine-conjugated forms) were also significantly ( P FDR <0.05) associated with more decreases in resting energy expenditure at 6 months. We found that reductions in two BA subtypes, glycocholic acid (GCA) and glycoursodeoxycholic acid (GUDCA), were consistently and significantly associated with improvements in energy metabolism, general and central adiposity, as well as body fat composition and visceral adipose tissue mass. Further, the initial (6-month) changes in several primary and secondary BAs (including GCA and GUDCA) were significantly predictive of the long-term successful weight loss (weight loss of more than 5% loss from the initial weight) at 2 years. Conclusions: Weight-loss diet-induced changes in circulating various BAs may be involved in improving general and central adiposity and energy metabolism. Changes in specific BA subtypes would be potential targets for improving regional adiposity and achieving successful weight-loss among patients with obesity.

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