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 lowcalorie weight-loss diets were significantly associated with improving adiposity, fat accumulation and energy metabolism, suggesting that specific BA subtypes would be Handling Editor: Luca Valenti predictive of long-term successful weight loss and individuals' response to the treatment of weight-loss diets.

Substantial Fat Loss in Physique Competitors Is Characterized by Increased Levels of Bile Acids, Very-Long Chain Fatty Acids, and Oxylipins

“…To add to the emerging body of evidence, lifestyle-induced weight loss among previously normal-weight physique athletes was shown by us to promote the accumulation of primary BA subsets, a shift towards non-12α-hydroxy dominant bile acid profile, together with a distinct loss of android fat mass, that most strongly explained observed changes in the fasting BA profile. Altogether, we suggest that loss of android fat mass and non-12α-hydroxy dominant bile acid profile may, in part, characterize the putatively advantageous metabolic status of female physique athletes following the weight loss period, although discordant findings from previous [ 19 , 20 , 25 , 26 , 27 ] and our study on the overall level of fasting BA alteration following weight loss need further insight to determine their role among normal-weight individuals. In the past, it has been suggested that moderate levels of BA (e.g., deoxycholic acid) concentrations may be optimal, whereas more extreme levels (low or high) may have deleterious effects.…”

“…However, other procedures that preserve the integrity of the intestine (i.e., laparoscopic sleeve gastrectomy, gastric banding) have not been associated with elevated BA levels despite similar weight loss and improved insulin sensitivity [ 20 , 21 , 24 ]. In overweight to obese individuals, contrary to findings from bariatric surgery-induced weight loss, diminished BA pools have been reported after lifestyle-induced weight loss [ 25 , 26 , 27 ]. Thus, it is plausible that bariatric surgery procedures (especially gastric bypass) lead to altered enterohepatic recirculation of BAs that counteract a weight loss-associated decrease in serum BA levels.…”