Role of Branched-Chain Amino Acid Metabolism in Type 2 Diabetes, Obesity, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease

Cuomo, Paola; Capparelli, Rosanna; Iannelli, Antonio; Iannelli, Domenico

doi:10.3390/ijms23084325

Cited by 44 publications

(36 citation statements)

References 65 publications

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“…The analyses in models 2c, 2d, 2f and 2g were potentially over-adjusted since it cannot be excluded that creatinine levels, lean mass or prevalent health conditions were affected, at least partly, by overall obesity and unhealthy fat accumulation [59][60][61][62]. Moreover, we additionally adjusted for plasma concentrations of BCAAs and/or tyrosine, which are correlated with plasma SAA concentrations and have been associated with obesity and fatty liver (e.g., [63,64],) (models 2 h-j). These analyses might be over-adjusted, since no known direct metabolic pathway links these amino acids and thus their correlation might be due to other factors.…”

Section: Discussionmentioning

confidence: 99%

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

et al. 2022

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Purpose Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods We examined cross-sectional subsets from the CODAM cohort (n = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results Methionine was associated with all measures of liver fat, e.g., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β = 0.19 (0.09, 0.28); DMS: β = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β = 0.15 (0.08, 0.23); DMS: β = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β = 0.16 (0.08, 0.25); DMS: β = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.

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Section: Discussionmentioning

confidence: 99%

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

et al. 2022

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“…BCAAs affect many physiological processes such as energy homeostasis, inflammation, and glycolysis ( 32 ). Currently, researches on BCAAs are mainly focused on metabolic diseases wherein elevated levels of BCAAs have been reported to be correlated with type 2 diabetes and obesity ( 33 ). Few studies have evaluated the association between BCAAs and AD.…”

Section: Discussionmentioning

confidence: 99%

Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab

Zhang

Wen²,

Hou³

et al. 2022

Front. Immunol.

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BackgroundAtopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4 and IL-13 receptors, has been widely used in AD because of its efficacy. However, metabolic changes occurring in patients with AD in response to dupilumab remains unknown. In this study, we integrated metabolomics and lipidomics analyses with clinical data to explore potential metabolic alterations associated with dupilumab therapeutic efficacy. In addition, we investigated whether the development of treatment side effects was linked to the dysregulation of metabolic pathways.MethodsA total of 33 patients with AD were included in the current study, with serum samples collected before and after treatment with dupilumab. Comprehensive metabolomic and lipidomic analyses have previously been developed to identify serum metabolites (including lipids) that vary among treatment groups. An orthogonal partial least squares discriminant analysis model was established to screen for differential metabolites and metabolites with variable importance in projection > 1 and p < 0.05 were considered potential metabolic biomarkers. MetaboAnalyst 5.0 was used to identify related metabolic pathways. Patients were further classified into two groups, well responders (n = 19) and poor responders (n = 14), to identify differential metabolites between the two groups.ResultsThe results revealed significant changes in serum metabolites before and after 16 weeks of dupilumab treatment. Variations in the metabolic profile were more significant in the well-responder group than in the poor-responder group. Pathway enrichment analysis revealed that differential metabolites derived from the well-responder group were mainly involved in glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis, the citrate cycle, arachidonic acid metabolism, pyrimidine metabolism, and sphingolipid metabolism.ConclusionSerum metabolic profiles of patients with AD varied significantly after treatment with dupilumab. Differential metabolites and their related metabolic pathways may provide clues for understanding the effects of dupilumab on patient metabolism.

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“…BCAAs are a class of essential amino acids which mainly depend on food intake and are also regulated by the gut microbiota. Multiple clinical studies found the level of BCAAs in plasma of patients with diabetes increased significantly ( Izundegui and Nayor, 2022 ), and the accumulation of BCAAs could inhibit the transport and utilization of pyruvic acid and fatty acid, promote glycogen synthesis and eventually lead to hyperglycemia ( Cuomo et al, 2022 ). Succinate is a multifunctional metabolite produced by the interaction between the host and the gut microbiota, which could play a role similar to hormones and signal molecules by binding with the succinate receptor-1 (SUCNR1) ( Canfora et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Global research trends on the links between the gut microbiota and diabetes between 2001 and 2021: A bibliometrics and visualized study

Zhang

Jin²,

Zhai³

et al. 2022

Front. Microbiol.

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BackgroundOver the past 20 years, evidence has suggested that gut microbiota plays an important role in metabolic homeostasis. The relationship between gut microbiota and diabetes has become the focus of considerable scientific interest. With the sharp increase in publications in this area, it is imperative to analyze the relevant articles using bibliometrics methods.MethodsPublications on “the gut microbiota and diabetes” were retrieved and downloaded from the Web of Science Core Collection database. Microsoft Excel 2020, VOSviewer, CiteSpace 5.8.R3 and Co-Occurrence 9.94 software were used for data analysis and visualization. Country/academic institution, journal, author, subject category, keyword and reference were analyzed thoroughly. The cutting-edge directions in this field were also determined by analyzing keywords and key articles.ResultsA total of 2,342 documents were included in the analysis; the number of articles in this field has increased yearly, particularly after 2010. China and the University of Copenhagen are the country and research institution associated with the largest number of publications. Nutrients have published 191 articles in this field, ranking first among highly productive journals in the number of publications. The researcher Cani PD affiliated with the University of Leuven, Belgium, published the greatest number of articles in this field between 2001 and 2021 and was also ranked as the first co-cited author and the largest contributor of highly cited papers in this field. Endocrinology & Metabolism was the most common subject category. Three of the most frequently found keywords, besides terms related to “microbiota” and “diabetes,” were “obesity,” “probiotics,” and “inflammation.” Akkermansia muciniphila, Faecalibacterium prausnitzii, trimethylamine n-oxide and branched-chain amino acids are intestinal bacteria or metabolites that have attracted more attention in recent years. Natural products represented by Chinese herbal medicine and some protein receptors or signaling pathways such as aryl hydrocarbon receptor, farnesoid X receptor and AMP-activated protein kinase were frontiers in this field.ConclusionOver the past two decades, the rapid development of research on the gut microbiota has deepened the understanding of the physiology and pathology of diabetes, providing new insights into different approaches to treatment. In the future, further interdisciplinary innovation, clinical transformation, and application may receive more attention.

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Role of Branched-Chain Amino Acid Metabolism in Type 2 Diabetes, Obesity, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease

Cited by 44 publications

References 65 publications

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab

Global research trends on the links between the gut microbiota and diabetes between 2001 and 2021: A bibliometrics and visualized study

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