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BCAA & oxidative stress & insulin resistance

Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
March 2017: Free Radical Biology & Medicine
Nancy F Butte, Yan Liu, Issa F Zakeri, Robert P Mohney, Nitesh Mehta, V Saroja Voruganti, Harald Göring, Shelley A Cole, Anthony G Comuzzie
BACKGROUND: Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. OBJECTIVES: We aimed to 1) identify metabolites that differ significantly between nonobese and obese Hispanic children; 2) collapse metabolites into principal components (PCs) associated with obesity and metabolic risk, specifically hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hyperuricemia; and 3) identify metabolites associated with energy expenditure and fat oxidation...
August 2015: American Journal of Clinical Nutrition
Joel S Burrill, Eric K Long, Brian Reilly, Yingfeng Deng, Ian M Armitage, Philipp E Scherer, David A Bernlohr
Inflammation plays a critical role in the pathology of obesity-linked insulin resistance and is mechanistically linked to the effects of macrophage-derived cytokines on adipocyte energy metabolism, particularly that of the mitochondrial branched-chain amino acid (BCAA) and tricarboxylic acid (TCA) pathways. To address the role of inflammation on energy metabolism in adipocytes, we used high fat-fed C57BL/6J mice and lean controls and measured the down-regulation of genes linked to BCAA and TCA cycle metabolism selectively in visceral but not in subcutaneous adipose tissue, brown fat, liver, or muscle...
March 2015: Molecular Endocrinology
Christopher J Lynch, Sean H Adams
Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage...
December 2014: Nature Reviews. Endocrinology
K Kaji, H Yoshiji, Y Ikenaka, R Noguchi, Y Aihara, Y Shirai, A Douhara, H Fukui
Angiogenesis plays a pivotal role in many pathological processes including chronic liver diseases. Various factors, such as renin-angiotensin-aldosterone system (RAAS), insulin resistance (IR), and reactive oxygen species (ROS) contribute reciprocally to promote angiogenesis. Blockade of RAAS by angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II (AngII) receptor blocker (ARB) markedly attenuates liver fibrosis and hepatocellular carcinoma (HCC) along with suppression of angiogenesis, IR, and ROS...
2012: Current Medicinal Chemistry
Sean H Adams
Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids...
November 2011: Advances in Nutrition
Susan C Connor, Michael K Hansen, Adam Corner, Randall F Smith, Terence E Ryan
Type 2 diabetes (T2D), one of the most common diseases in the western world, is characterized by insulin resistance and impaired beta-cell function but currently it is difficult to determine the precise pathophysiology in individual T2D patients. Non-targeted metabolomics technologies have the potential for providing novel biomarkers of disease and drug efficacy, and are increasingly being incorporated into biomarker exploration studies. Contextualization of metabolomics results is enhanced by integration of study data from other platforms, such as transcriptomics, thus linking known metabolites and genes to relevant biochemical pathways...
May 2010: Molecular BioSystems
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