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BCAA & insulin resistance

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https://www.readbyqxmd.com/read/28323986/chronic-intranasal-insulin-does-not-affect-hepatic-lipids-but-lowers-circulating-bcaas-in-healthy-male-subjects
#1
Thomas Scherer, Peter Wolf, Sabina Smajis, Melania Gaggini, Martina Hackl, Amalia Gastaldelli, Peter Klimek, Elisa Einwallner, Rodrig Marculescu, Anton Luger, Clemens Fürnsinn, Siegfried Trattnig, Christoph Buettner, Martin Krššák, Michael Krebs
Context: Non-alcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Objective: Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans...
January 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28238968/changes-in-macroautophagy-chaperone-mediated-autophagy-and-mitochondrial-metabolism-in-murine-skeletal-and-cardiac-muscle-during-aging
#2
Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K Singh, Rohit A Sinha, Adam B Salmon, Paul M Yen
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28184960/genetic-evidence-of-a-causal-effect-of-insulin-resistance-on-branched-chain-amino-acid-levels
#3
Yuvaraj Mahendran, Anna Jonsson, Christian T Have, Kristine H Allin, Daniel R Witte, Marit E Jørgensen, Niels Grarup, Oluf Pedersen, Tuomas O Kilpeläinen, Torben Hansen
AIMS/HYPOTHESIS: Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. METHODS: We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort...
February 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#4
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
https://www.readbyqxmd.com/read/27883272/circulating-adipocyte-derived-exosomal-micrornas-associated-with-decreased-insulin-resistance-after-gastric-bypass
#5
Monica J Hubal, Evan P Nadler, Sarah C Ferrante, Matthew D Barberio, Jung-Hyuk Suh, Justin Wang, G Lynis Dohm, Walter J Pories, Michelle Mietus-Snyder, Robert J Freishtat
OBJECTIVE: Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte-derived exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis. METHODS: African American female subjects with obesity (N = 6; age: 38...
January 2017: Obesity
https://www.readbyqxmd.com/read/27765690/isocaloric-diets-high-in-animal-or-plant-protein-reduce-liver-fat-and-inflammation-in-individuals-with-type-2-diabetes
#6
Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insulin resistance. We investigated the effects of diets high in animal protein (AP) vs plant protein (PP), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
February 2017: Gastroenterology
https://www.readbyqxmd.com/read/27754422/effect-of-green-tea-extract-on-systemic-metabolic-homeostasis-in-diet-induced-obese-mice-determined-via-rna-seq-transcriptome-profiles
#7
Ji-Young Choi, Ye Jin Kim, Ri Ryu, Su-Jung Cho, Eun-Young Kwon, Myung-Sook Choi
Green tea (GT) has various health effects, including anti-obesity properties. However, the multiple molecular mechanisms of the effects have not been fully determined. The aim of this study was to elucidate the anti-obesity effects of GT via the analysis of its metabolic and transcriptional responses based on RNA-seq profiles. C57BL/6J mice were fed a normal, high-fat (60% energy as fat), or high-fat + 0.25% (w/w) GT diet for 12 weeks. The GT extract ameliorated obesity, hepatic steatosis, dyslipidemia, and insulin resistance in diet-induced obesity (DIO) mice...
October 14, 2016: Nutrients
https://www.readbyqxmd.com/read/27730694/acylcarnitines-as-markers-of-exercise-associated-fuel-partitioning-xenometabolism-and-potential-signals-to-muscle-afferent-neurons
#8
Jie Zhang, Alan R Light, Charles L Hoppel, Caitlin Campbell, Carol J Chandler, Dustin J Burnett, Elaine C Souza, Gretchen A Casazza, Ronald W Hughen, Nancy L Keim, John W Newman, Gary R Hunter, Jose R Fernandez, W Timothy Garvey, Mary-Ellen Harper, Oliver Fiehn, Sean H Adams
What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover...
January 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/27689005/defects-in-muscle-branched-chain-amino-acid-oxidation-contribute-to-impaired-lipid-metabolism
#9
Carles Lerin, Allison B Goldfine, Tanner Boes, Manway Liu, Simon Kasif, Jonathan M Dreyfuss, Ana Luisa De Sousa-Coelho, Grace Daher, Irini Manoli, Justin R Sysol, Elvira Isganaitis, Niels Jessen, Laurie J Goodyear, Kirk Beebe, Walt Gall, Charles P Venditti, Mary-Elizabeth Patti
OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27642608/the-relationship-between-branched-chain-amino-acid-related-metabolomic-signature-and-insulin-resistance-a-systematic-review
#10
REVIEW
Xue Zhao, Qing Han, Yujia Liu, Chenglin Sun, Xiaokun Gang, Guixia Wang
Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27591698/associations-between-branched-chain-amino-acid-intake-and-biomarkers-of-adiposity-and-cardiometabolic-health-independent-of-genetic-factors-a-twin-study
#11
Amy Jennings, Alex MacGregor, Tess Pallister, Tim Spector, Aedín Cassidy
BACKGROUND: Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics. METHODS: In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, high-sensitivity C-reactive protein (hs-CRP) and lipids...
November 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27517054/using-metabolomic-profiles-as-biomarkers-for-insulin-resistance-in-childhood-obesity-a-systematic-review
#12
REVIEW
Xue Zhao, Xiaokun Gang, Yujia Liu, Chenglin Sun, Qing Han, Guixia Wang
A growing body of evidence has shown the intimate relationship between metabolomic profiles and insulin resistance (IR) in obese adults, while little is known about childhood obesity. In this review, we searched available papers addressing metabolomic profiles and IR in obese children from inception to February 2016 on MEDLINE, Web of Science, the Cochrane Library, ClinicalTrials.gov, and EMASE. HOMA-IR was applied as surrogate markers of IR and related metabolic disorders at both baseline and follow-up. To minimize selection bias, two investigators independently completed this work...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27488662/ketoisocaproic-acid-a-metabolite-of-leucine-suppresses-insulin-stimulated-glucose-transport-in-skeletal-muscle-cells-in-a-bcat2-dependent-manner
#13
Mahshid Moghei, Pegah Tavajohi-Fini, Brendan Beatty, Olasunkanmi A J Adegoke
Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport (P < 0...
September 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27409811/human-gut-microbes-impact-host-serum-metabolome-and-insulin-sensitivity
#14
Helle Krogh Pedersen, Valborg Gudmundsdottir, Henrik Bjørn Nielsen, Tuulia Hyotylainen, Trine Nielsen, Benjamin A H Jensen, Kristoffer Forslund, Falk Hildebrand, Edi Prifti, Gwen Falony, Emmanuelle Le Chatelier, Florence Levenez, Joel Doré, Ismo Mattila, Damian R Plichta, Päivi Pöhö, Lars I Hellgren, Manimozhiyan Arumugam, Shinichi Sunagawa, Sara Vieira-Silva, Torben Jørgensen, Jacob Bak Holm, Kajetan Trošt, Karsten Kristiansen, Susanne Brix, Jeroen Raes, Jun Wang, Torben Hansen, Peer Bork, Søren Brunak, Matej Oresic, S Dusko Ehrlich, Oluf Pedersen
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids...
July 21, 2016: Nature
https://www.readbyqxmd.com/read/27408778/branched-chain-amino-acid-restriction-in-zucker-fatty-rats-improves-muscle-insulin-sensitivity-by-enhancing-efficiency-of-fatty-acid-oxidation-and-acyl-glycine-export
#15
Phillip J White, Amanda L Lapworth, Jie An, Liping Wang, Robert W McGarrah, Robert D Stevens, Olga Ilkayeva, Tabitha George, Michael J Muehlbauer, James R Bain, Jeff K Trimmer, M Julia Brosnan, Timothy P Rolph, Christopher B Newgard
OBJECTIVE: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. METHODS: Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES)...
July 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27376324/the-emerging-role-of-branched-chain-amino-acids-in-insulin-resistance-and-metabolism
#16
REVIEW
Mee-Sup Yoon
Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or type 2 diabetes mellitus (T2DM)...
July 1, 2016: Nutrients
https://www.readbyqxmd.com/read/27373162/a-role-for-timp3-in-microbiota-driven-hepatic-steatosis-and-metabolic-dysfunction
#17
Maria Mavilio, Valentina Marchetti, Marta Fabrizi, Robert Stöhr, Arianna Marino, Viviana Casagrande, Loredana Fiorentino, Marina Cardellini, Ben Kappel, Ivan Monteleone, Celine Garret, Alessandro Mauriello, Giovanni Monteleone, Alessio Farcomeni, Remy Burcelin, Rossella Menghini, Massimo Federici
The effect of gut microbiota on obesity and insulin resistance is now recognized, but the underlying host-dependent mechanisms remain poorly undefined. We find that tissue inhibitor of metalloproteinase 3 knockout (Timp3(-/-)) mice fed a high-fat diet exhibit gut microbiota dysbiosis, an increase in branched chain and aromatic (BCAA) metabolites, liver steatosis, and an increase in circulating soluble IL-6 receptors (sIL6Rs). sIL6Rs can then activate inflammatory cells, such as CD11c(+) cells, which drive metabolic inflammation...
July 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27313851/associations-between-plasma-branched-chain-amino-acids-%C3%AE-aminoisobutyric-acid-and-body-composition
#18
Annemarie Rietman, Takara L Stanley, Clary Clish, Vamsi Mootha, Marco Mensink, Steven K Grinspoon, Hideo Makimura
Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women...
2016: Journal of Nutritional Science
https://www.readbyqxmd.com/read/27289540/amino-acid-changes-during-transition-to-a-vegan-diet-supplemented-with-fish-in-healthy-humans
#19
Amany Elshorbagy, Fredrik Jernerén, Marianne Basta, Caroline Basta, Cheryl Turner, Maram Khaled, Helga Refsum
PURPOSE: To explore whether changes in dietary protein sources can lower plasma branched-chain amino acids (BCAAs), aromatic amino acids and sulfur amino acids (SAAs) that are often elevated in the obese, insulin-resistant state and in type 2 diabetes. METHODS: Thirty-six subjects (mean age 31 ± 2 years) underwent a voluntary abstinence from meat, poultry, eggs, and dairy products for 6 weeks, while enriching the diet with fish, in fulfillment of a religious fast...
June 11, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27252163/linking-gut-microbiota-and-inflammation-to-obesity-and-insulin-resistance
#20
REVIEW
M J A Saad, A Santos, P O Prada
Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota...
July 2016: Physiology
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