Highlights
- •Changes in various bile acid (BA) subtypes showed differential effects on improvements in glucose and insulin resistance.
- •Habitual dietary fat intakes modified the relations between changes in BA metabolism and improved glucose metabolism.
- •Changes in BA subtypes may be potential targets to achieve better outcomes during weight-loss dietary interventions.
Abstract
Objective
Various primary and secondary bile acids (BAs) may play pivotal roles in glucose/insulin
metabolism. We investigated whether changes in specific BA subtypes were associated
with long-term changes in glucose and insulin sensitivity.
Methods
This study included 515 adults with overweight or obesity who participated in a 2-year
intervention study of weight-loss diets with different macronutrient intakes. Circulating
primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were
measured at baseline and 6 months after the interventions. We analyzed associations
of changes in BA subtypes with two-year changes in fasting glucose, insulin, and insulin
resistance (HOMA-IR).
Results
Greater decreases in primary and secondary BA subtypes induced by the interventions
were significantly associated with greater reductions of fasting insulin and HOMA-IR
at 6 months, showing various effects across the BA subtypes. The reductions of specific
BA subtypes (chenodeoxycholate [CDCA], taurocholate [TCA], taurochenodeoxycholate
[TCDCA], and taurodeoxycholate [TDCA]) were significantly related to improved glucose
levels at 6 months. The initial (6-month) decreases in primary and secondary BA subtypes
(glycochenodeoxycholate [GCDCA], TCDCA, and glycoursodeoxycholate [GUDCA]) were also
significantly associated with long-term improvements in glucose and insulin metabolism
over 2 years. We found significant interactions between dietary fat intake and changes
in the BA subtypes for changes in glucose metabolism (Pinteraction < 0.05).
Conclusions
Weight-loss diet-induced changes in distinct subtypes of circulating BAs were associated
with improved glucose metabolism and insulin sensitivity in adults with overweight
or obesity. Dietary fat intake may modify the associations of changes in BA metabolism
with glucose metabolism.
Graphical abstract
Graphical Abstract
Abbreviations:
BA (bile acid), BMI (body mass index), HOMA-IR (homeostasis model assessment-of-insulin resistance), POUNDS Lost (the Preventing Overweight Using Novel Dietary Strategies), MS (mass spectrometry), CA (cholate), CDCA (chenodeoxycholate), GCA (glycocholate), TCA (taurocholate), GCDCA (glycochenodeoxycholate), TCDCA (taurochenodeoxycholate), DCA (deoxycholate), LCA (lithocholate), UDCA (ursodeoxycholate), GDCA (glycodeoxycholate), TDCA (taurodeoxycholate), GLCA (glycolithocholate), GUDCA (glycoursodeoxycholate), THDCA (taurohyodeoxycholate), TUDCA (tauroursodeoxycholate), FDR (False Discovery Rate), FXR (farnesoid X receptor), TGR (takeda G protein-coupled receptor 5), GLP-1 (glucagon-like peptide-1)Keywords
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Article info
Publication history
Published online: September 15, 2022
Accepted:
September 13,
2022
Received:
June 9,
2022
Footnotes
☆Trial registration number: The trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT00072995. Identifier: NCT00072995).
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
