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Integrated Remodeling of Gut-Liver Metabolism Induced by Moderate Protein Restriction Contributes to Improvement of Insulin Sensitivity.

ABSTRACT: SCOPE:Protein restriction (PR) is beneficial for relieving metabolic disorders and aging-related diseases. However, extreme PR could result in malnutrition due to severe deficiency of essential amino acids. Therefore, the effect of moderate PR on insulin sensitivity is investigated. METHODS AND RESULTS:The growing and adult pigs are subjected to moderate PR by 15-30%. Plasma insulin concentration and insulin resistance index HOMA-IR are significantly decreased upon moderate PR. Furthermore, IRS1/PI3K/AKT pathway in the basal state is enhanced in both liver and skeletal muscle. The adapted metabolism in the liver upon moderate PR is in support of improving insulin sensitivity. The liver shares a coordinated metabolic adaption in terms of energy metabolism and amino acid metabolism with the small intestine. Particularly, alteration of the metabolic footprint appeared in the portal venous blood, representing metabolites to be absorbed into liver after intestinal metabolism, is also in favor of improvement of insulin sensitivity. CONCLUSION:In summary, the study proves that moderate PR could improve insulin sensitivity from childhood to adulthood in a pig model, and sheds a new light on the role of integrated remodeling of gut and liver metabolism in the improved insulin sensitivity induced by moderate PR.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6646914 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Integrated Remodeling of Gut-Liver Metabolism Induced by Moderate Protein Restriction Contributes to Improvement of Insulin Sensitivity.

Zhang Xin X Qiu Kai K Wang Liqi L Xu Doudou D Yin Jingdong J

Molecular nutrition & food research 20180826 19

<h4>Scope</h4>Protein restriction (PR) is beneficial for relieving metabolic disorders and aging-related diseases. However, extreme PR could result in malnutrition due to severe deficiency of essential amino acids. Therefore, the effect of moderate PR on insulin sensitivity is investigated.<h4>Methods and results</h4>The growing and adult pigs are subjected to moderate PR by 15-30%. Plasma insulin concentration and insulin resistance index HOMA-IR are significantly decreased upon moderate PR. Fu ...[more]

PMID: 30030886

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Project description:BACKGROUND:Diets high in cereal-fiber (HCF) have been shown to improve whole-body insulin sensitivity. In search for potential mechanisms we hypothesized that a supplemented HCF-diet influences the composition of the human gut microbiota and/or biomarkers of colonic carbohydrate fermentation. METHODS:We performed a randomized controlled 18-week intervention in group-matched overweight participants. Fecal samples of 69 participants receiving isoenergetic HCF (cereal-fiber 43 g/day), or control (cereal-fiber 14 g/day), or high-protein (HP, 28% of energy-intake, cereal-fiber 14 g/day), or moderately high cereal fiber/protein diets (MIX; protein 23% of energy-intake, cereal-fiber 26 g/day) with comparable fat contents were investigated for diet-induced changes of dominant groups of the gut microbiota, and of fecal short-chain fatty-acids (SCFA) including several of their proposed targets, after 0, 6, and 18-weeks of dietary intervention. In vitro fermentation of the cereal fiber extracts as used in the HCF and MIX diets was analyzed using gas chromatography. Diet-induced effects on whole-body insulin-sensitivity were measured using euglycaemic-hyperinsulinemic clamps and re-calculated in the here investigated subset of n = 69 participants that provided sufficient fecal samples on all study days. RESULTS:Gut microbiota groups and biomarkers of colonic fermentation were comparable between groups at baseline (week 0). No diet-induced differences were detected between groups during this isoenergetic intervention, neither in the full model nor in uncorrected subgroup-analyses. The cereal-fiber extract as used for preparation of the supplements in the HCF and MIX groups did not support in vitro fermentation. Fecal acetate, propionate, and butyrate concentrations remained unchanged, as well as potential targets of increased SCFA, whereas valerate increased after 6-weeks in the HP-group only (p = 0.037). Insulin-sensitivity significantly increased in the HCF-group from week-6 (baseline M-value 3.8 ± 0.4 vs 4.3 ± 0.4 mg·kg-1·min-1, p = 0.015; full model 0-18-weeks, treatment-x-time interaction, p = 0.046). CONCLUSIONS:Changes in the composition of the gut microbiota and/or markers of colonic carbohydrate fermentation did not contribute explaining the observed early onset and significant improvement of whole-body insulin sensitivity with the here investigated HCF-diet. TRIAL REGISTRATION:This trial was registered at http://www.clinicaltrials.gov as NCT00579657.

Dataset Information

Integrated Remodeling of Gut-Liver Metabolism Induced by Moderate Protein Restriction Contributes to Improvement of Insulin Sensitivity.

Publications

Integrated Remodeling of Gut-Liver Metabolism Induced by Moderate Protein Restriction Contributes to Improvement of Insulin Sensitivity.

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