TY - JOUR
T1 - Reversal of insulin resistance in people with obesity by lifestyle-induced weight loss does not impact the proportion of circulating 12α-hydroxylated bile acids
AU - Palmiotti, Anna
AU - Berk, Kirsten A.
AU - Koehorst, Martijn
AU - Hovingh, Milaine V.
AU - Pranger, Alle T.
AU - van Faassen, Martijn
AU - de Boer, Jan Freark
AU - van der Valk, Eline S.
AU - van Rossum, Elisabeth F.C.
AU - Mulder, Monique T.
AU - Kuipers, Folkert
N1 - Publisher Copyright:
© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2024/9
Y1 - 2024/9
N2 - Aim: Bile acids (BAs) are implicated in the pathogenesis of several metabolic syndrome-related diseases, including insulin resistance (IR) and type 2 diabetes (T2D). It has been reported that IR and T2D are associated with an increased ratio of 12α/non-12α-hydroxylated BAs in the circulating BA pool. It is, however, unknown whether the improvement of insulin sensitivity inversely affects BA composition in humans. Therefore, we assessed whether lifestyle-induced weight loss induces changes in BA metabolism in people with obesity, with or without T2D, and if these changes are associated with metabolic parameters. Materials and Methods: Individual BAs and C4 were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry in plasma samples collected from two cohorts of people with obesity (OB) and with T2D and obesity (T2D), before and after a lifestyle intervention. Results: Lifestyle-induced weight loss improved glycaemic control in both cohorts, with plasma BA concentrations not affected by the lifestyle interventions. The ratio of 12α/non-12α-hydroxylated BAs remained unchanged in OB (p =.178) and even slightly increased upon intervention in T2D (p =.0147). Plasma C4 levels were unaffected in OB participants (p =.20) but significantly reduced in T2D after intervention (p =.0003). There were no significant correlations between the ratio of 12α/non-12α-hydroxylated BAs and glucose, insulin, or homeostatic model assessment-IR, nor in plasma triglycerides, low-density lipoprotein cholesterol, lipoprotein (a) in the T2D cohort. Conclusions: Lifestyle-induced weight loss did improve glycaemic control but did not affect BA concentrations. Improvements in insulin sensitivity were not associated with changes in BA parameters in people with obesity, with or without T2D.
AB - Aim: Bile acids (BAs) are implicated in the pathogenesis of several metabolic syndrome-related diseases, including insulin resistance (IR) and type 2 diabetes (T2D). It has been reported that IR and T2D are associated with an increased ratio of 12α/non-12α-hydroxylated BAs in the circulating BA pool. It is, however, unknown whether the improvement of insulin sensitivity inversely affects BA composition in humans. Therefore, we assessed whether lifestyle-induced weight loss induces changes in BA metabolism in people with obesity, with or without T2D, and if these changes are associated with metabolic parameters. Materials and Methods: Individual BAs and C4 were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry in plasma samples collected from two cohorts of people with obesity (OB) and with T2D and obesity (T2D), before and after a lifestyle intervention. Results: Lifestyle-induced weight loss improved glycaemic control in both cohorts, with plasma BA concentrations not affected by the lifestyle interventions. The ratio of 12α/non-12α-hydroxylated BAs remained unchanged in OB (p =.178) and even slightly increased upon intervention in T2D (p =.0147). Plasma C4 levels were unaffected in OB participants (p =.20) but significantly reduced in T2D after intervention (p =.0003). There were no significant correlations between the ratio of 12α/non-12α-hydroxylated BAs and glucose, insulin, or homeostatic model assessment-IR, nor in plasma triglycerides, low-density lipoprotein cholesterol, lipoprotein (a) in the T2D cohort. Conclusions: Lifestyle-induced weight loss did improve glycaemic control but did not affect BA concentrations. Improvements in insulin sensitivity were not associated with changes in BA parameters in people with obesity, with or without T2D.
KW - cohort study
KW - dietary intervention
KW - glycaemic control
KW - liver
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85197305267&partnerID=8YFLogxK
U2 - 10.1111/dom.15754
DO - 10.1111/dom.15754
M3 - Article
C2 - 38957937
AN - SCOPUS:85197305267
SN - 1462-8902
VL - 26
SP - 4019
EP - 4029
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 9
ER -