Serum amino acid concentrations are modified by age, insulin resistance, and BCAT2 rs11548193 and BCKDH rs45500792 polymorphisms in subjects with obesity

Guizar-Heredia, Rocío; Tovar, Armando R.; Granados‐Portillo, Omar; Pichardo-Ontiveros, Edgar; Flores-López, Adriana; González-Salazar, Luis E.; Arteaga-Sánchez, L.; Medina‐Vera, Isabel; Orozco-Ruiz, Ximena; Torres, Nimbe; Noriega, Lilia G.; Guevara‐Cruz, Martha

doi:10.1016/j.clnu.2021.01.037

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…By contrast, elevated plasma BCAA levels have been found to have an adverse effect on glucose metabolism and to be associated with type 2 diabetes in humans and rodents [ 28 , 29 ]. The amount of BCAAs increases in the presence of insulin-resistant polymorphisms [ 30 ]. Mitochondrial BCAA enzymes in white adipose tissue are decreased under conditions of obesity and diabetes, suggesting that adipose tissue regulates BCAA levels in the blood [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans

Kuroiwa

Hamaoka-Fuse

Sugimoto

et al. 2021

JCM

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This study examined the relationship between plasma amino acid (AA) concentrations, including branched-chain AAs, and brown adipose tissue density (BAT-d). One hundred and seventy-three subjects (69 men, 104 women) aged 22–68 years were recruited during the winter season. AAs were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. The total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, was assessed using near-infrared time-resolved spectroscopy. Anthropometric parameters, including age, percentage of body fat, and visceral fat, were evaluated. Factors associated with higher (≥74 µM) or lower (<74 µM) [total-Hb]sup were investigated by multiple logistic regression models that included AA concentrations alone (model 1) or AA concentrations and anthropometric parameters (model 2) as independent variables. When adjusted for the false discovery rate, [total-Hb]sup was positively correlated with glycine and asparagine levels in men and with the serine level in both men and women and was negatively correlated with the branched-chain AA concentration in men. Models 1 and 2 correlated with higher or lower BAT-d for men (r = 0.73, p = 0.015) and women (r = 0.58, p = 0.079) and for men (r = 0.82, p = 0.0070) and women (r = 0.70, p = 0.020), respectively. A combination of anthropometric parameters and plasma AA concentrations could be a reliable biomarker for higher and lower BAT-d.

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Section: Discussionmentioning

confidence: 99%

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans

Kuroiwa

Hamaoka-Fuse

Sugimoto

et al. 2021

JCM

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“…As expected, these increases in plasma BCAAs were associated with decreased oxidation by BCKD [ 52 ]. Note that in the study of Guizar-Heredia et al [ 51 ], in obese patients, the non-common blood BCAA-raising alleles BCAT2 rs11548193 and BCKDH rs45500792 were associated with higher BCAA levels, and the difference was maintained after adjustment for BMI and insulin resistance.…”

Section: Blood Bcaas As Biomarkers Of Metabolic Statusmentioning

confidence: 92%

“…It should be noted that, here too, various factors can affect this relationship. Indeed, in the above-mentioned study of Guizar-Heredia et al [ 51 ], there was an effect of age and insulin resistance on plasma BCAAs, resulting in similar BCAA concentrations between young patients without insulin resistance and those over 30 years with insulin resistance.…”

Section: Blood Bcaas As Biomarkers Of Metabolic Statusmentioning

confidence: 99%

“…An additional cross-sectional analysis [ 50 ] indicated that the BMI explained 11.6% of BCAA variability. In a study in 487 obese patients with (homeostatic model assessment insulin resistance index (HOMA IR) > 2.5) or without insulin resistance, Guizar-Heredia et al [ 51 ] described an association between plasma BCAAs and age (higher leucine below 30 years old). A meta-analysis of three genome-wide association studies of plasma BCAAs identified five genomic regions, the strongest association being with a sequence upstream of the BCKD phosphatase PPM1K gene.…”

Section: Blood Bcaas As Biomarkers Of Metabolic Statusmentioning

confidence: 99%

“…Interestingly, some human studies show differences between animal and plant proteins. In the study of Guizar-Heredia et al [ 51 ], BCAA levels were positively correlated with animal protein intake and negatively with that of vegetable protein. Hamaya et al [ 50 ], in their cross-sectional analysis of the Women’s Health Study, also showed an association of plasma BCAAs with animal but not vegetable protein intake.…”

Section: Blood Bcaas As Biomarkers Of Metabolic Statusmentioning

confidence: 99%

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Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity

2022

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For more than a decade, there has been a wide debate about the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, with, on the one hand, the supporters of their anabolic effects and, on the other hand, those who suspect them of promoting insulin resistance. Indeed, the role of leucine in the postprandial activation of protein synthesis has been clearly established, even though supplementation studies aimed at taking advantage of this property are rather disappointing. Furthermore, there is ample evidence of an association between the elevation of their plasma concentrations and insulin resistance or the risk of developing type 2 diabetes, although there are many confounding factors, starting with the level of animal protein consumption. After a summary of their metabolism and anabolic properties, we analyze in this review the factors likely to increase the plasma concentrations of BCAAs, including insulin-resistance. After an analysis of supplementation or restriction studies in search of a direct role of BCAAs in insulin resistance, we discuss an indirect role through some of their metabolites: branched-chain keto acids, C3 and C5 acylcarnitines, and hydroxyisobutyrate. Overall, given the importance of insulin in the metabolism of these amino acids, it is very likely that small alterations in insulin sensitivity are responsible for a reduction in their catabolism long before the onset of impaired glucose tolerance.

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Plasma amino acid signatures define types of pediatric diabetes

Tosur¹,

Hsu²,

Deen³

et al. 2023

Clinical Nutrition ESPEN

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Serum amino acid concentrations are modified by age, insulin resistance, and BCAT2 rs11548193 and BCKDH rs45500792 polymorphisms in subjects with obesity

Cited by 7 publications

References 30 publications

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans

Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity

Plasma amino acid signatures define types of pediatric diabetes

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