A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance

Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain amino acids and diabetes. Epidemiol...

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Published in:	Nature medicine Vol. 22; no. 4; pp. 421 - 426
Main Authors:	Jang, Cholsoon, Oh, Sungwhan F, Wada, Shogo, Rowe, Glenn C, Liu, Laura, Chan, Mun Chun, Rhee, James, Hoshino, Atsushi, Kim, Boa, Ibrahim, Ayon, Baca, Luisa G, Kim, Esl, Ghosh, Chandra C, Parikh, Samir M, Jiang, Aihua, Chu, Qingwei, Forman, Daniel E, Lecker, Stewart H, Krishnaiah, Saikumari, Rabinowitz, Joshua D, Weljie, Aalim M, Baur, Joseph A, Kasper, Dennis L, Arany, Zoltan
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.04.2016 Nature Publishing Group
Subjects:	13/1 13/106 13/109 13/44 13/51 13/89 14/19 14/34 14/5 38/39 59 59/5 631/337 631/80/304 64 64/60 692/163/2743/137/773 82 Accumulation Amino acids Amino Acids, Branched-Chain - metabolism Animals Biological transport Biomedicine Cancer Research Development and progression Diabetes Experimental data Fatty acids Fatty Acids - genetics Fatty Acids - metabolism Fluctuations Genetic aspects Health aspects Humans Hydroxybutyrates - metabolism Infectious Diseases Insulin - genetics Insulin - metabolism Insulin resistance Insulin Resistance - genetics letter Lipids Metabolic Diseases Metabolites Mice Mice, Inbred NOD Molecular Medicine Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Neurosciences Obesity - genetics Obesity - metabolism Obesity - pathology Pathogenesis Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Properties Transcription factors Transcription Factors - biosynthesis Transcription Factors - genetics
ISSN:	1078-8956, 1546-170X, 1546-170X
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Abstract	Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain amino acids and diabetes. Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear 1 , 2 , 3 . Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species 4 , a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a ), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
AbstractList	Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. Epidemiological and experimental data implicate branchedchain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear (1-3). Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species (4), a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGCla (also known as PGC-1α; encoded by Ppargcla), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1 alpha ; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1 alpha to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain amino acids and diabetes. Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear 1 , 2 , 3 . Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species 4 , a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a ), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear1, 2, 3. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species4, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
Audience	Academic
Author	Rhee, James Chu, Qingwei Kasper, Dennis L Forman, Daniel E Baca, Luisa G Hoshino, Atsushi Lecker, Stewart H Chan, Mun Chun Wada, Shogo Oh, Sungwhan F Jang, Cholsoon Liu, Laura Kim, Boa Jiang, Aihua Baur, Joseph A Arany, Zoltan Weljie, Aalim M Krishnaiah, Saikumari Kim, Esl Rowe, Glenn C Ghosh, Chandra C Parikh, Samir M Ibrahim, Ayon Rabinowitz, Joshua D
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26950361$$D View this record in MEDLINE/PubMed
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Cites_doi	10.1038/nm.2307 10.1016/j.celrep.2013.04.023 10.1182/blood-2011-08-375816 10.1210/er.2006-0037 10.1016/j.metabol.2014.01.006 10.1016/j.cmet.2009.02.002 10.1016/j.cmet.2013.12.003 10.1371/journal.pone.0129084 10.1021/cb300194b 10.1016/j.cmet.2006.12.003 10.1016/j.cmet.2012.01.024 10.1038/nature08945 10.1073/pnas.0810339105 10.1023/A:1016611824696 10.1038/ncomms8078 10.1056/NEJMra1011035 10.1007/s00125-015-3656-y 10.1016/j.cardfail.2014.03.007 10.1016/S0387-7604(01)00196-6 10.1038/nature06613 10.1016/j.cmet.2013.12.014 10.1038/nature00904 10.1242/jcs.103.1.23 10.1016/S0022-2275(20)38227-4
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References	Giesbertz (CR16) 2015; 58 Shulman (CR4) 2014; 371 Darland, D'Amore (CR23) 2001; 4 Hagberg (CR8) 2010; 464 Abbott, Hughes, Revest, Greenwood (CR19) 1992; 103 Handschin, Spiegelman (CR6) 2006; 27 Titchenell, Chu, Monks, Birnbaum (CR24) 2015; 6 Avogaro, Bier (CR15) 1989; 30 Arany (CR7) 2008; 451 Roberts (CR9) 2014; 19 Hatazawa (CR12) 2015; 10 Henkin (CR13) 2012; 7 Arany (CR11) 2007; 5 Sasaki (CR18) 2001; 23 Newgard (CR2) 2009; 9 Forman (CR25) 2014; 20 Newgard (CR3) 2012; 15 Choi (CR14) 2008; 105 Rowe (CR21) 2013; 3 Sawada (CR22) 2014; 19 Lin (CR10) 2002; 418 Mullen, Ohlendieck (CR17) 2010; 25 Xie (CR20) 2012; 119 Chan, Arany (CR5) 2014; 63 Wang (CR1) 2011; 17 CB Newgard (BFnm4057_CR2) 2009; 9 Z Arany (BFnm4057_CR7) 2008; 451 LD Roberts (BFnm4057_CR9) 2014; 19 Z Arany (BFnm4057_CR11) 2007; 5 CS Choi (BFnm4057_CR14) 2008; 105 P Giesbertz (BFnm4057_CR16) 2015; 58 TJ Wang (BFnm4057_CR1) 2011; 17 M Sasaki (BFnm4057_CR18) 2001; 23 Y Hatazawa (BFnm4057_CR12) 2015; 10 N Sawada (BFnm4057_CR22) 2014; 19 AH Henkin (BFnm4057_CR13) 2012; 7 C Handschin (BFnm4057_CR6) 2006; 27 GI Shulman (BFnm4057_CR4) 2014; 371 DC Darland (BFnm4057_CR23) 2001; 4 DE Forman (BFnm4057_CR25) 2014; 20 J Lin (BFnm4057_CR10) 2002; 418 NJ Abbott (BFnm4057_CR19) 1992; 103 PM Titchenell (BFnm4057_CR24) 2015; 6 Z Xie (BFnm4057_CR20) 2012; 119 CE Hagberg (BFnm4057_CR8) 2010; 464 GC Rowe (BFnm4057_CR21) 2013; 3 CB Newgard (BFnm4057_CR3) 2012; 15 A Avogaro (BFnm4057_CR15) 1989; 30 E Mullen (BFnm4057_CR17) 2010; 25 MC Chan (BFnm4057_CR5) 2014; 63 20127051 - Int J Mol Med. 2010 Mar;25(3):445-58 22928772 - ACS Chem Biol. 2012 Nov 16;7(11):1884-91 11377004 - Brain Dev. 2001 Jul;23(4):243-5 25963408 - Nat Commun. 2015 May 12;6:7078 23707060 - Cell Rep. 2013 May 30;3(5):1449-56 1429907 - J Cell Sci. 1992 Sep;103 ( Pt 1):23-37 22411873 - Blood. 2012 May 3;119(18):4321-32 2614280 - J Lipid Res. 1989 Nov;30(11):1811-7 26988615 - Nat Rev Endocrinol. 2016 May;12(5):249 25229917 - N Engl J Med. 2014 Sep 18;371(12):1131-41 17189205 - Cell Metab. 2007 Jan;5(1):35-46 19066218 - Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19926-31 26114427 - PLoS One. 2015 Jun 26;10 (6):e0129084 26058503 - Diabetologia. 2015 Sep;58(9):2133-43 24704539 - J Card Fail. 2014 Jun;20(6):422-30 18599867 - Circ Res. 2008 Aug 15;103(4):360-8 19356713 - Cell Metab. 2009 Apr;9(4):311-26 12181572 - Nature. 2002 Aug 15;418(6899):797-801 24559845 - Metabolism. 2014 Apr;63(4):441-51 17018837 - Endocr Rev. 2006 Dec;27(7):728-35 21423183 - Nat Med. 2011 Apr;17(4):448-53 18288196 - Nature. 2008 Feb 21;451(7181):1008-12 24411942 - Cell Metab. 2014 Jan 7;19(1):96-108 22560213 - Cell Metab. 2012 May 2;15(5):606-14 20228789 - Nature. 2010 Apr 8;464(7290):917-21 11824373 - Angiogenesis. 2001;4(1):11-20
References_xml	– volume: 17 start-page: 448 year: 2011 end-page: 453 ident: CR1 article-title: Metabolite profiles and the risk of developing diabetes publication-title: Nat. Med. doi: 10.1038/nm.2307 – volume: 3 start-page: 1449 year: 2013 end-page: 1456 ident: CR21 article-title: Disconnecting mitochondrial content from respiratory chain capacity in PGC-1-deficient skeletal muscle publication-title: Cell Reports doi: 10.1016/j.celrep.2013.04.023 – volume: 119 start-page: 4321 year: 2012 end-page: 4332 ident: CR20 article-title: Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome) publication-title: Blood doi: 10.1182/blood-2011-08-375816 – volume: 27 start-page: 728 year: 2006 end-page: 735 ident: CR6 article-title: Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism publication-title: Endocr. Rev. doi: 10.1210/er.2006-0037 – volume: 63 start-page: 441 year: 2014 end-page: 451 ident: CR5 article-title: The many roles of PGC-1α in muscle—recent developments publication-title: Metabolism doi: 10.1016/j.metabol.2014.01.006 – volume: 9 start-page: 311 year: 2009 end-page: 326 ident: CR2 article-title: A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance publication-title: Cell Metab. doi: 10.1016/j.cmet.2009.02.002 – volume: 19 start-page: 96 year: 2014 end-page: 108 ident: CR9 article-title: β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.12.003 – volume: 10 start-page: e0129084 year: 2015 ident: CR12 article-title: Metabolomic analysis of the skeletal muscle of mice overexpressing PGC-1α publication-title: PLoS One doi: 10.1371/journal.pone.0129084 – volume: 7 start-page: 1884 year: 2012 end-page: 1891 ident: CR13 article-title: Real-time noninvasive imaging of fatty acid uptake publication-title: ACS Chem. Biol. doi: 10.1021/cb300194b – volume: 5 start-page: 35 year: 2007 end-page: 46 ident: CR11 article-title: The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle publication-title: Cell Metab. doi: 10.1016/j.cmet.2006.12.003 – volume: 15 start-page: 606 year: 2012 end-page: 614 ident: CR3 article-title: Interplay between lipids and branched-chain amino acids in development of insulin resistance publication-title: Cell Metab. doi: 10.1016/j.cmet.2012.01.024 – volume: 103 start-page: 23 year: 1992 end-page: 37 ident: CR19 article-title: Development and characterisation of a rat brain capillary endothelial culture: towards an blood-brain barrier publication-title: J. Cell Sci. – volume: 464 start-page: 917 year: 2010 end-page: 921 ident: CR8 article-title: Vascular endothelial growth factor B controls endothelial fatty acid uptake publication-title: Nature doi: 10.1038/nature08945 – volume: 105 start-page: 19926 year: 2008 end-page: 19931 ident: CR14 article-title: Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0810339105 – volume: 4 start-page: 11 year: 2001 end-page: 20 ident: CR23 article-title: TGFβ is required for the formation of capillary-like structures in three-dimensional cocultures of 10T1/2 and endothelial cells publication-title: Angiogenesis doi: 10.1023/A:1016611824696 – volume: 6 start-page: 7078 year: 2015 ident: CR24 article-title: Hepatic insulin signalling is dispensable for suppression of glucose output by insulin publication-title: Nat. Commun. doi: 10.1038/ncomms8078 – volume: 371 start-page: 1131 year: 2014 end-page: 1141 ident: CR4 article-title: Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1011035 – volume: 58 start-page: 2133 year: 2015 end-page: 2143 ident: CR16 article-title: Metabolite profiling in plasma and tissues of and mice identifies novel markers of obesity and type 2 diabetes publication-title: Diabetologia doi: 10.1007/s00125-015-3656-y – volume: 20 start-page: 422 year: 2014 end-page: 430 ident: CR25 article-title: Analysis of skeletal muscle gene expression patterns and the impact of functional capacity in patients with systolic heart failure publication-title: J. Card. Fail. doi: 10.1016/j.cardfail.2014.03.007 – volume: 25 start-page: 445 year: 2010 end-page: 458 ident: CR17 article-title: Proteomic profiling of non-obese type 2 diabetic skeletal muscle publication-title: Int. J. Mol. Med. – volume: 23 start-page: 243 year: 2001 end-page: 245 ident: CR18 article-title: A severely brain-damaged case of 3-hydroxyisobutyric aciduria publication-title: Brain Dev. doi: 10.1016/S0387-7604(01)00196-6 – volume: 451 start-page: 1008 year: 2008 end-page: 1012 ident: CR7 article-title: HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α publication-title: Nature doi: 10.1038/nature06613 – volume: 19 start-page: 246 year: 2014 end-page: 258 ident: CR22 article-title: Endothelial PGC-1α mediates vascular dysfunction in diabetes publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.12.014 – volume: 418 start-page: 797 year: 2002 end-page: 801 ident: CR10 article-title: Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres publication-title: Nature doi: 10.1038/nature00904 – volume: 30 start-page: 1811 year: 1989 end-page: 1817 ident: CR15 article-title: Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects publication-title: J. Lipid Res. – volume: 119 start-page: 4321 year: 2012 ident: BFnm4057_CR20 publication-title: Blood doi: 10.1182/blood-2011-08-375816 – volume: 20 start-page: 422 year: 2014 ident: BFnm4057_CR25 publication-title: J. Card. Fail. doi: 10.1016/j.cardfail.2014.03.007 – volume: 103 start-page: 23 year: 1992 ident: BFnm4057_CR19 publication-title: J. Cell Sci. doi: 10.1242/jcs.103.1.23 – volume: 105 start-page: 19926 year: 2008 ident: BFnm4057_CR14 publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0810339105 – volume: 27 start-page: 728 year: 2006 ident: BFnm4057_CR6 publication-title: Endocr. Rev. doi: 10.1210/er.2006-0037 – volume: 10 start-page: e0129084 year: 2015 ident: BFnm4057_CR12 publication-title: PLoS One doi: 10.1371/journal.pone.0129084 – volume: 19 start-page: 246 year: 2014 ident: BFnm4057_CR22 publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.12.014 – volume: 464 start-page: 917 year: 2010 ident: BFnm4057_CR8 publication-title: Nature doi: 10.1038/nature08945 – volume: 19 start-page: 96 year: 2014 ident: BFnm4057_CR9 publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.12.003 – volume: 451 start-page: 1008 year: 2008 ident: BFnm4057_CR7 publication-title: Nature doi: 10.1038/nature06613 – volume: 23 start-page: 243 year: 2001 ident: BFnm4057_CR18 publication-title: Brain Dev. doi: 10.1016/S0387-7604(01)00196-6 – volume: 5 start-page: 35 year: 2007 ident: BFnm4057_CR11 publication-title: Cell Metab. doi: 10.1016/j.cmet.2006.12.003 – volume: 7 start-page: 1884 year: 2012 ident: BFnm4057_CR13 publication-title: ACS Chem. Biol. doi: 10.1021/cb300194b – volume: 371 start-page: 1131 year: 2014 ident: BFnm4057_CR4 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1011035 – volume: 25 start-page: 445 year: 2010 ident: BFnm4057_CR17 publication-title: Int. J. Mol. Med. – volume: 17 start-page: 448 year: 2011 ident: BFnm4057_CR1 publication-title: Nat. Med. doi: 10.1038/nm.2307 – volume: 3 start-page: 1449 year: 2013 ident: BFnm4057_CR21 publication-title: Cell Reports doi: 10.1016/j.celrep.2013.04.023 – volume: 58 start-page: 2133 year: 2015 ident: BFnm4057_CR16 publication-title: Diabetologia doi: 10.1007/s00125-015-3656-y – volume: 6 start-page: 7078 year: 2015 ident: BFnm4057_CR24 publication-title: Nat. Commun. doi: 10.1038/ncomms8078 – volume: 63 start-page: 441 year: 2014 ident: BFnm4057_CR5 publication-title: Metabolism doi: 10.1016/j.metabol.2014.01.006 – volume: 15 start-page: 606 year: 2012 ident: BFnm4057_CR3 publication-title: Cell Metab. doi: 10.1016/j.cmet.2012.01.024 – volume: 4 start-page: 11 year: 2001 ident: BFnm4057_CR23 publication-title: Angiogenesis doi: 10.1023/A:1016611824696 – volume: 9 start-page: 311 year: 2009 ident: BFnm4057_CR2 publication-title: Cell Metab. doi: 10.1016/j.cmet.2009.02.002 – volume: 30 start-page: 1811 year: 1989 ident: BFnm4057_CR15 publication-title: J. Lipid Res. doi: 10.1016/S0022-2275(20)38227-4 – volume: 418 start-page: 797 year: 2002 ident: BFnm4057_CR10 publication-title: Nature doi: 10.1038/nature00904 – reference: 1429907 - J Cell Sci. 1992 Sep;103 ( Pt 1):23-37 – reference: 17189205 - Cell Metab. 2007 Jan;5(1):35-46 – reference: 11377004 - Brain Dev. 2001 Jul;23(4):243-5 – reference: 22411873 - Blood. 2012 May 3;119(18):4321-32 – reference: 22928772 - ACS Chem Biol. 2012 Nov 16;7(11):1884-91 – reference: 19356713 - Cell Metab. 2009 Apr;9(4):311-26 – reference: 25963408 - Nat Commun. 2015 May 12;6:7078 – reference: 18288196 - Nature. 2008 Feb 21;451(7181):1008-12 – reference: 26114427 - PLoS One. 2015 Jun 26;10 (6):e0129084 – reference: 11824373 - Angiogenesis. 2001;4(1):11-20 – reference: 22560213 - Cell Metab. 2012 May 2;15(5):606-14 – reference: 23707060 - Cell Rep. 2013 May 30;3(5):1449-56 – reference: 26988615 - Nat Rev Endocrinol. 2016 May;12(5):249 – reference: 2614280 - J Lipid Res. 1989 Nov;30(11):1811-7 – reference: 24704539 - J Card Fail. 2014 Jun;20(6):422-30 – reference: 25229917 - N Engl J Med. 2014 Sep 18;371(12):1131-41 – reference: 24411942 - Cell Metab. 2014 Jan 7;19(1):96-108 – reference: 21423183 - Nat Med. 2011 Apr;17(4):448-53 – reference: 18599867 - Circ Res. 2008 Aug 15;103(4):360-8 – reference: 12181572 - Nature. 2002 Aug 15;418(6899):797-801 – reference: 20228789 - Nature. 2010 Apr 8;464(7290):917-21 – reference: 17018837 - Endocr Rev. 2006 Dec;27(7):728-35 – reference: 20127051 - Int J Mol Med. 2010 Mar;25(3):445-58 – reference: 19066218 - Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19926-31 – reference: 24559845 - Metabolism. 2014 Apr;63(4):441-51 – reference: 26058503 - Diabetologia. 2015 Sep;58(9):2133-43
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Snippet	Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite... Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie... Epidemiological and experimental data implicate branchedchain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie...
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Title	A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance
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