Abstract
Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45–55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672).
Highlights
May increase serum BA, FGF-19 and GLP-1 levels, is coupled with rapid resolution of insulin resistance and improved insulin secretion[9,12,13,14]
It remains unknown whether therapeutically altering of serum BA levels and/or composition may represent a useful target for interventions aiming to improve glucose metabolism in insulin resistant individuals[9,10,16]
Prospective clinical studies evaluating the orchestrated changes of serum BA composition and associated gut-derived hormone levels (e.g. GLP-1, FGF-19) during conventional weight loss are lacking
Summary
May increase serum BA, FGF-19 and GLP-1 levels, is coupled with rapid resolution of insulin resistance and improved insulin secretion[9,12,13,14]. Plasma BA composition was recently suggested as early biomarker for insulin resistance in healthy non-obese individuals[15]. It remains unknown whether therapeutically altering of serum BA levels and/or composition may represent a useful target for interventions aiming to improve glucose metabolism in insulin resistant individuals[9,10,16]. Prospective clinical studies evaluating the orchestrated changes of serum BA composition and associated gut-derived hormone levels (e.g. GLP-1, FGF-19) during conventional (lifestyle-induced) weight loss are lacking. To address the question how conventional weight loss affects BA metabolism in prediabetic individuals we prospectively determined the changes and interrelations of 15 endogenous BA species, clinical and metabolic parameters, and the intestinal hormones GLP-1 and FGF-19 following lifestyle-induced weight loss in 74 well-defined individuals with MetS in a prospective study
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