Changes in bile acid subtypes and long‐term successful weight‐loss in response to weight‐loss diets: The POUNDS lost trial

Abstract Background and Aims Primary bile acids (BAs) are synthesized in the liver and secondary BAs result from intestinal microbial activity. Different subtypes of BAs may be involved in regulating adiposity and energy homeostasis. We examined how changes in circulating BA subtypes induced by weight‐loss diets were associated with improvements in adiposity, regional fat deposition and energy metabolism among overweight and obese adults. Methods The study included 551 subjects who participated in a 2‐year weight‐loss diet intervention trial. Circulating 14 BA subtypes (primary and secondary unconjugated BAs and their taurine‐/glycine‐conjugates) were measured at baseline and 6 months. Associations of changes in BAs with changes in weight, waist circumference, resting energy expenditure (REE), body fat composition and fat distribution were evaluated. Results Greater decreases in primary BAs (cholate and chenodeoxycholate) and secondary BAs (deoxycholate and lithocholate) and their conjugates (except for glycolithocholate) were associated with more decreases in weight and waist circumference at 6 months ( P ‐after‐false‐discovery‐rate‐correction [P FDR ] < . 05 ). We found that changes in glycocholate and glycoursodeoxycholate were consistently associated with reductions of general and central adiposity, REE, whole‐body fat and visceral adipose tissue ( P FDR < .05). Further, the initial (6‐month) changes in BA subtypes were differently predictive of successful weight loss over 2 years. Conclusions The decreases in primary and secondary BA subtypes after eating low‐calorie weight‐loss diets were significantly associated with improving adiposity, fat accumulation and energy metabolism, suggesting that specific BA subtypes would be predictive of long‐term successful weight loss and individuals' response to the treatment of weight‐loss diets.