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Whole Grain Qingke Attenuates High-Fat Diet-Induced Obesity in Mice With Alterations in Gut Microbiota and Metabolite Profile.

ABSTRACT: Whole grain Qingke (WGQK) displays anti-obesity and lipid-lowering properties; however, the underlying mechanism remains elusive. This study investigated the alteration of gut microbiota composition and metabolite profile induced by WGQK intervention in mice through the integration of 16S ribosomal RNA (rRNA) sequencing and an untargeted metabolomics study. C57BL/6J male mice were fed a normal control diet (NC), high-fat diet (HFD), and HFD plus 30% WGQK (HFD+QK) for 16 weeks. The WGQK intervention decreased body weight gain, glucose tolerance, and serum lipid levels, and alleviated liver function damage induced by HFD. Moreover, WGQK changed gut microbiota composition and enriched specific genera such as Akkermansia, Bifidobacterium, and Lactobacillus. Fecal metabolomics analysis indicated that WGQK enhanced the abundance of tryptophan metabolism-related metabolites (indole, 3-indoleacetic acid, indole acetic acid (IAA), 5-hydroxyindole-3-acetic acid), histidine metabolism-related metabolites (histamine), and some unsaturated fatty acids (oleic acid, 9,10-dihydroxy-12Z-octadecenoic acid, and alpha-linolenic acid). Spearman correlation analysis revealed that these metabolites were negatively correlated with obesity-related parameters and positively correlated with the gut genera enriched by WGQK. Moreover, WGQK promoted the expression of Cholesterol 7α-hydroxylase (CYP7A1) responsible for primary bile acids production, accompanied by a decline in intestinal FXR-FGF15 expression levels. The transcript levels of two genes associated with lipogenesis, such as lipid fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were also decreased in the HFD+QK group. Overall, our results suggest interactions between gut microbial shifts and host amino acid/lipid metabolism, and shed light on the mechanisms underlying the anti-obesity effect of WGQK.

SUBMITTER: Li X

PROVIDER: S-EPMC8688713 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Objectives We investigated the effect of consuming a whole-grain diet on whole-body protein metabolism compared to a macronutrient-matched refined-grain diet in adults with overweight/obesity using labelled amino acids (ClinicalTrials.gov Identifier: NCT01411540). Methods We conducted a randomized, controlled crossover trial in 14 adults with overweight/obesity (age: 40 ± 7 yrs, BMI: 33 ± 5 kg/m2) in which isocaloric, macronutrient-matched whole-grain (WG) and refined-grain (RG) diets were fully provided for two 8-week periods (with a 10-week washout period). Diets differed only in the inclusion of whole grains (50 g/1000 kcal). Body composition was measured via DEXA. Whole-body protein kinetics were assessed before and after each diet in the fasted state (13C-Leucine, primed, constant infusion) and over 24 hours (15N-Glycine, bolus). Protein kinetics were normalized to fat-free mass (FFM). Results Both diets resulted in mild weight loss (WG: −2.0 ± 2.5 kg; RG: −2.9 ± 3.3 kg; both P = 0.01 compared to baseline). Fasted-state leucine kinetics revealed greater protein synthesis (WG: 205 ± 61 µmol/kgFFM/hr; RG: 178 ± 36 µmol/kgFFM/hr; P = 0.04) and protein breakdown (WG: 235 ± 68 µmol/kgFFM/hr; RG: 203 ± 40 µmol/kgFFM/hr, P = 0.03) on a WG vs RG diet. This resulted in a more negative fasted-state net balance on a WG diet (WG: −30 ± 8 µmol/kg/hr; RG: −25 ± 6 µmol/kg/hr, P = 0.02). In contrast, 24-hour whole-body protein turnover measured by the end-product method (15N-Glycine), revealed greater protein synthesis (WG: 316 ± 135 mg protein/kgFFM/hr; RG: 250 ± 94 mg protein/kgFFM/hr) with no difference in protein breakdown, yielding a more positive 24-hr net balance on a WG diet (WG: 31 ± 21 mg protein/kgFFM/hr; RG: 10 ± 34 mg protein/kgFFM/hr). Conclusions A whole-grain diet increases whole-body leucine flux and results in a greater 24-hr net protein balance in adults with overweight/obesity compared to a refined-grain diet. This trial suggests whole-grains have an independent effect on protein metabolism and may benefit adults with overweight/obesity. Funding Sources This research was supported by the NIH (UL1 RR024989, T32DK007319 (JPK); T32AT004094 (JTM – trainee)) and an investigator-initiated grant from Nestle (JPK). Nestle Product Technology Center and Cereal Partners Worldwide provided the study meals and foods.

Project description:BackgroundThere are limited data from randomized control trials to support or refute the contention that whole-grains can enhance protein metabolism in humans.ObjectivesTo examine: 1) the clinical effects of a whole-grain diet on whole-body protein turnover; 2) the cellular effects of whole-grains on protein synthesis in skeletal muscle cells; and 3) the population effects of whole-grain intake on age-related muscle loss.MethodsAdults with overweight/obesity (n = 14; age = 40 ± 7 y; BMI = 33 ± 5 kg/m2) were recruited into a crossover, randomized controlled trial (NCT01411540) in which isocaloric, macronutrient-matched whole-grain and refined-grain diets were fully provisioned for two 8-wk periods. Diets differed only in the presence of whole-grains (50 g/1000 kcal). Whole-body protein kinetics were assessed at baseline and after each diet in the fasted-state (13C-leucine) and integrated over 24 h (15N-glycine). In vitro studies using C2C12 cells assessed global protein synthesis by surface sensing of translation and anabolic signaling by Western blot. Complementary epidemiological assessments using the NHANES database assessed the effect of whole-grain intake on muscle function assessed by gait speed in older adults (n = 2783).ResultsIntegrated 24-h net protein balance was 3-fold higher on a whole-grain diet compared with a refined-grain diet (P = 0.04). A whole-grain wheat extract increased submaximal rates of global protein synthesis (27%, P < 0.05) in vitro. In a large sample of older adults, whole-grain intake was associated with greater muscle function (OR = 0.92; 95% CI: 0.86, 0.98).ConclusionsConsuming 50 g/1000 kcal whole-grains per day promotes greater protein turnover and enhances net protein balance in adults. Whole-grains impact skeletal muscle at the cellular level, and are associated with greater muscle function in older adults. Collectively, these data point to a new mechanism whereby whole-grain consumption favorably enhances protein turnover and improves health outcomes.This clinical trial is registered on clinicaltrials.gov (identifier: NCT01411540).

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Whole Grain Qingke Attenuates High-Fat Diet-Induced Obesity in Mice With Alterations in Gut Microbiota and Metabolite Profile.

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