Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance - PubMed (original) (raw)

Randomized Controlled Trial

Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Martin O Weickert et al. Nutr Diabetes. 2018.

Abstract

Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic-hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1

Fig. 1. Comparison of bile acids (BA) circulating concentrations between obese (n = 43; white bars) and overweight (n = 29; black bars) participants in the pooled cohort, irrespective of the dietary groups.

The graph shows changes relative to the baseline values (week 0) after a 6 weeks and b 18 weeks of dietary intervention. *Statistically significant at alpha < 0.05. ∑All: sum of all BA; ∑Prim: sum of primary BA; ∑Sec: sum of secondary BA; ∑Tert: sum of tertiary BA; 12-α: 12-α hydroxyl BA; non 12-α: non 12-α hydroxylated BA; 12-α/non 12-α: ratio of 12-α hydroxyl BA to non 12-α hydroxylated BA; Conj: conjugated BA; Unconj: unconjugated BA; Conj/Unconj: ratio of conjugated to unconjugated BA

Fig. 2

Fig. 2. Comparison of circulating bile acids (BA) concentrations, relative to baseline value at week 0, after 6 and 18 weeks between obese (ob) and overweight (ow) subjects in the 4 diet groups

: a Control at 6 weeks (ow/ob: n = 10/10). b Control at 18 weeks (ow/ob: n = 10/10). c High cereal fiber (HCF) at 6 weeks (ow/ob: n = 5/10). d HCF at 18 weeks (ow/ob: n = 5/10). e High protein (HP) at 6 weeks (ow/ob: n = 6/12); f HP at 18 weeks (ow/ob: n = 6/12). g Mixed-diet (MIX) group at 6 weeks (ow/ob: n = 8/11). h MIX at 18 weeks (ow/ob: n = 8/11). Black bars: overweight; white bars: obese. *Statistically significant at alpha < 0.05. ∑All: sum of all BA; ∑Prim: sum of primary BA; ∑Sec: sum of secondary BA; ∑Tert: sum of tertiary BA; 12-α: 12-α hydroxyl BA; non 12-α: non 12-α hydroxylated BA; 12-α/non 12-α: ratio of 12-α hydroxyl BA to non 12-α hydroxylated BA; Conj: conjugated BA; Unconj: unconjugated BA; Conj/Unconj: ratio of conjugated to unconjugated BA

Fig. 3

Fig. 3. Partial correlation plots for circulating bile acids (BA) vs. fibroblast growth factor-19 (FGF-19) plasma concentrations, corrected for age and body mass index (BMI), measured after 18 weeks of dietary intervention.

a All study subjects: all BA pooled vs. FGF-19 (n = 68). b All study subjects: 12-alpha BA vs. FGF-19 (n = 68). c Control group only: all pooled BA vs. FGF-19 (n = 18). d High cereal fiber group (HCF) only: all pooled BA vs. FGF-19 (n = 15). e High protein (HP) group only: all pooled BA vs. FGF-19 (n = 17). f Mixed-diet (MIX) group only: all pooled BA vs. FGF-19 (n = 18). R correlation coefficient

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