Diabetes and branched‐chain amino acids: <scp>W</scp>hat is the link?

Bloomgarden, Zachary T.

doi:10.1111/1753-0407.12645

Cited by 180 publications

(137 citation statements)

References 43 publications

(44 reference statements)

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“…These findings were also observed in our study, BCAA had positively related to total cholesterol and glucose, which were reduced in inulin groups. The risk of future T2D was substantially increased with the elevation of a small cluster of circulating amino acids, including BCAAs and aromatic amino acids [54]. As the activation of the mammalian target of rapamycin (mTOR) and its downstream effectors, S6 kinase and insulin receptor substrate-1, the elevating BCAA may disrupt insulin signaling, thus triggering T2D [54,55].…”

Section: Discussionmentioning

confidence: 99%

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

Zhang

Xia

et al. 2020

Microorganisms

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Inulin (INU) is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. However, whether and how gut microbiota in its regulation contributes to host metabolism has yet to be investigated. We conduct this study to examine the possible associations between the gut microbiota and circulating gut microbiota–host co-metabolites induced by inulin interventions. Plasma and intestinal site samples were collected from the pigs that have consumed inulin diet for 60 days. High-throughput sequencing was adopted for microbial composition, and the GC-TOF-MS-based metabolomics were used to characterize featured plasma metabolites upon inulin intervention. Integrated multi-omics analyses were carried out to establish microbiota–host interaction. Inulin consumption decreased the total cholesterol (p = 0.04) and glucose (p = 0.03) level in serum. Greater β-diversity was observed in the cecum and colon of inulin-fed versus that of control-fed pigs (p < 0.05). No differences were observed in the ileum. In the cecum, 18 genera were altered by inulin, followed by 17 in the colon and 6 in the ileum. Inulin increased propionate, and isobutyrate concentrations but decreased the ratio of acetate to propionate in the cecum, and increased total short fatty acids, valerate, and isobutyrate concentrations in the colon. Metabolomic analysis reveals that indole-3-propionic acid (IPA) was significantly higher, and the branched-chain amino acids (BCAA), L-valine, L-isoleucine, and L-leucine are significantly lower in the inulin groups. Mantel test and integrative analysis revealed associations between plasma metabolites (e.g., IPA, BCAA, L-tryptophan) and inulin-responsive cecal microbial genera. These results indicate that the inulin has regional effects on the intestine microbiome in pigs, with the most pronounced effects occurring in the cecum. Moreover, cecum microbiota plays a pivotal role in the modulation of circulating host metabolites upon inulin intervention

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Section: Discussionmentioning

confidence: 99%

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

Zhang

Xia

et al. 2020

Microorganisms

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“…The exact mechanism responsible remains unclear, but may be connected to changes in the intestinal microenvironment 33 or the metabolism of gut flora, such as that of short-chain fatty acids, which have been suggested to strengthen the gut barrier, 34 or branched-chain amino acids, which have also been associated with increased INS sensitivity after bariatric surgery. 35 Recently, Thaiss et al 36 revealed that improved glycemia may contribute to restored gut integrity through a mechanism involving the glucose transported GLUT2 on the basolateral membranes of enterocytes. Based on this, we speculate that the improvement in gut permeability can be partly attributed to the rapid control of glucose levels after RYGB surgery.…”

Section: Discussionmentioning

confidence: 99%

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Guo

Liu

et al. 2019

Journal of Diabetes

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Background Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux‐en‐Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram‐negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. Methods Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham‐operated group pair‐fed with the RY group; and (c) a sham‐operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate‐dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)‐1, occludin, and claudin‐1 were assessed 10 weeks postoperatively. Results Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin‐1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO‐1, occludin, and claudin‐1 expression. Conclusions The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram‐negative bacteria.

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“…As another example, BCAA have been described to be altered in human diabetes, a risk factor for Alzheimer's disease [242]. Preclinical studies have shown that the accumulation of these amino acids in brain promotes the phosphorylation of Tau proteins, which are involved in the development of Alzheimer [243]. Thus, the identification of alterations in these biomarkers and their precursors would be of high relevance.…”

Section: Future Perspectivesmentioning

confidence: 99%

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

et al. 2020

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The metabolic syndrome is a multifactorial disease developed due to accumulation and chronification of several risk factors associated with disrupted metabolism. The early detection of the biomarkers by NMR spectroscopy could be helpful to prevent multifactorial diseases. The exposure of each risk factor can be detected by traditional molecular markers but the current biomarkers have not been enough precise to detect the primary stages of disease. Thus, there is a need to obtain novel molecular markers of pre-disease stages. A promising source of new molecular markers are metabolomics standing out the research of biomarkers in NMR approaches. An increasing number of nutritionists integrate metabolomics into their study design, making nutrimetabolomics one of the most promising avenues for improving personalized nutrition. This review highlight the major five risk factors associated with metabolic syndrome and related diseases including carbohydrate dysfunction, dyslipidemia, oxidative stress, inflammation, and gut microbiota dysbiosis. Together, it is proposed a profile of metabolites of each risk factor obtained from NMR approaches to target them using personalized nutrition, which will improve the quality of life for these patients.

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Diabetes and branched‐chain amino acids: What is the link?

Cited by 180 publications

References 43 publications

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

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