{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:22:08Z","timestamp":1788916928533,"version":"build-2803163510"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Inflammation, lipotoxicity and mitochondrial dysfunction have been implicated in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes. However, how these factors are intertwined in the development of obesity\/insulin resistance remains unclear. Here, we examine the role of mitochondrial fat oxidation on lipid-induced inflammation in skeletal muscle. We used skeletal muscle-specific\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    knockout mouse model where the inhibition of mitochondrial fatty acid oxidation results in accumulation of lipid metabolites in muscle and elevated circulating free fatty acids. Gene expression of pro-inflammatory cytokines, chemokines, and cytokine- and members of TLR-signalling pathways were decreased in\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    <jats:sup>m\u2212\/\u2212<\/jats:sup>\n                    muscle. Inflammatory signalling pathways were not activated when evaluated by multiplex and immunoblot analysis. In addition, the inflammatory response to fatty acids was reduced in primary muscle cells derived from\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    <jats:sup>m\u2212\/\u2212<\/jats:sup>\n                    mice. Gene expression of\n                    <jats:italic>Cd11c<\/jats:italic>\n                    , the M1 macrophage marker, was decreased; while\n                    <jats:italic>Cd206<\/jats:italic>\n                    , the M2 macrophage marker, was increased in skeletal muscle of\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    <jats:sup>m\u2212\/\u2212<\/jats:sup>\n                    mice. Finally, expression of pro-inflammatory markers was decreased in white adipose tissue of\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    <jats:sup>m\u2212\/\u2212<\/jats:sup>\n                    mice. We show that the inflammatory response elicited by elevated intracellular lipids in skeletal muscle is repressed in\n                    <jats:italic>Cpt1b<\/jats:italic>\n                    <jats:sup>m\u2212\/\u2212<\/jats:sup>\n                    mice, strongly supporting the hypothesis that mitochondrial processing of fatty acids is essential for the lipid-induction of inflammation in muscle.\n                  <\/jats:p>","DOI":"10.1038\/srep37941","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T06:13:02Z","timestamp":1480313582000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Mitochondrial fat oxidation is essential for lipid-induced inflammation in skeletal muscle in mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Jaycob D.","family":"Warfel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrellita M.","family":"Bermudez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamra M.","family":"Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujoy","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie M.","family":"Elks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Mynatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolormaa","family":"Vandanmagsar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,28]]},"reference":[{"key":"BFsrep37941_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1172\/JCI77812","volume":"126","author":"VT Samuel","year":"2016","unstructured":"Samuel, V. T. & Shulman, G. I. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest 126, 12\u201322 (2016).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2337\/diabetes.51.1.7","volume":"51","author":"JD McGarry","year":"2002","unstructured":"McGarry, J. D. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51, 7\u201318 (2002).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1172\/JCI10583","volume":"106","author":"GI Shulman","year":"2000","unstructured":"Shulman, G. I. Cellular mechanisms of insulin resistance. J Clin Invest 106, 171\u2013176 (2000).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR4","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1146\/annurev.med.53.082901.104057","volume":"53","author":"RH Unger","year":"2002","unstructured":"Unger, R. H. Lipotoxic diseases. Annu Rev Med 53, 319\u2013336 (2002).","journal-title":"Annu Rev Med"},{"key":"BFsrep37941_CR5","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1172\/JCI25102","volume":"115","author":"KE Wellen","year":"2005","unstructured":"Wellen, K. E. & Hotamisligil, G. S. Inflammation, stress, and diabetes. J Clin Invest 115, 1111\u20131119 (2005).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR6","doi-asserted-by":"publisher","first-page":"10297","DOI":"10.1074\/jbc.M212307200","volume":"278","author":"JA Chavez","year":"2003","unstructured":"Chavez, J. A. et al. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 278, 10297\u201310303 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep37941_CR7","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1096\/fj.14-255901","volume":"29","author":"C Aguer","year":"2015","unstructured":"Aguer, C. et al. Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB J 29, 336\u2013345 (2015).","journal-title":"FASEB J"},{"key":"BFsrep37941_CR8","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","volume":"7","author":"TR Koves","year":"2008","unstructured":"Koves, T. R. et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7, 45\u201356 (2008).","journal-title":"Cell Metab"},{"key":"BFsrep37941_CR9","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1172\/JCI117600","volume":"94","author":"DE Kelley","year":"1994","unstructured":"Kelley, D. E. & Simoneau, J. A. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 94, 2349\u20132356 (1994).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR10","doi-asserted-by":"publisher","first-page":"542","DOI":"10.2337\/diabetes.53.3.542","volume":"53","author":"M Gaster","year":"2004","unstructured":"Gaster, M., Rustan, A. C., Aas, V. & Beck-Nielsen, H. Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin: evidence from cultured myotubes. Diabetes 53, 542\u2013548 (2004).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR11","doi-asserted-by":"publisher","first-page":"E1039","DOI":"10.1152\/ajpendo.2000.279.5.E1039","volume":"279","author":"JY Kim","year":"2000","unstructured":"Kim, J. Y., Hickner, R. C., Cortright, R. L., Dohm, G. L. & Houmard, J. A. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279, E1039\u20131044 (2000).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFsrep37941_CR12","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.2337\/db06-S002","volume":"55","author":"K Morino","year":"2006","unstructured":"Morino, K., Petersen, K. F. & Shulman, G. I. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55 Suppl 2, S9\u2013S15 (2006).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR13","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1126\/science.1104343","volume":"307","author":"BB Lowell","year":"2005","unstructured":"Lowell, B. B. & Shulman, G. I. Mitochondrial dysfunction and type 2 diabetes. Science 307, 384\u2013387 (2005).","journal-title":"Science"},{"key":"BFsrep37941_CR14","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.2337\/db12-1612","volume":"62","author":"BH Goodpaster","year":"2013","unstructured":"Goodpaster, B. H. Mitochondrial deficiency is associated with insulin resistance. Diabetes 62, 1032\u20131035 (2013).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nrendo.2015.189","volume":"12","author":"DE Lackey","year":"2016","unstructured":"Lackey, D. E. & Olefsky, J. M. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol 12, 15\u201328 (2016).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep37941_CR16","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1159\/000212758","volume":"55","author":"M Zeyda","year":"2009","unstructured":"Zeyda, M. & Stulnig, T. M. Obesity, inflammation, and insulin resistance\u2013a mini-review. Gerontology 55, 379\u2013386 (2009).","journal-title":"Gerontology"},{"key":"BFsrep37941_CR17","first-page":"181","volume":"3","author":"JF Tanti","year":"2012","unstructured":"Tanti, J. F., Ceppo, F., Jager, J. & Berthou, F. Implication of inflammatory signaling pathways in obesity-induced insulin resistance. Front Endocrinol (Lausanne) 3, 181 (2012).","journal-title":"Front Endocrinol (Lausanne)"},{"key":"BFsrep37941_CR18","doi-asserted-by":"publisher","first-page":"E453","DOI":"10.1152\/ajpendo.00553.2012","volume":"304","author":"NJ Pillon","year":"2013","unstructured":"Pillon, N. J., Bilan, P. J., Fink, L. N. & Klip, A. Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications. Am J Physiol Endocrinol Metab 304, E453\u2013465 (2013).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFsrep37941_CR19","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1172\/JCI200319246","volume":"112","author":"SP Weisberg","year":"2003","unstructured":"Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 1796\u20131808 (2003).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR20","doi-asserted-by":"publisher","first-page":"E1300","DOI":"10.1152\/ajpendo.90885.2008","volume":"296","author":"V Varma","year":"2009","unstructured":"Varma, V. et al. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab 296, E1300\u20131310 (2009).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFsrep37941_CR21","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.coph.2009.07.004","volume":"9","author":"JF Tanti","year":"2009","unstructured":"Tanti, J. F. & Jager, J. Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr Opin Pharmacol 9, 753\u2013762 (2009).","journal-title":"Curr Opin Pharmacol"},{"key":"BFsrep37941_CR22","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1172\/JCI57132","volume":"121","author":"CN Lumeng","year":"2011","unstructured":"Lumeng, C. N. & Saltiel, A. R. Inflammatory links between obesity and metabolic disease. J Clin Invest 121, 2111\u20132117 (2011).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR23","doi-asserted-by":"publisher","first-page":"E3300","DOI":"10.1073\/pnas.1418560112","volume":"112","author":"SE Wicks","year":"2015","unstructured":"Wicks, S. E. et al. Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism. Proc Natl Acad Sci USA 112, E3300\u20133309 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep37941_CR24","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1016\/j.celrep.2016.04.057","volume":"15","author":"B Vandanmagsar","year":"2016","unstructured":"Vandanmagsar, B. et al. Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle. Cell Rep 15, 1686\u20131699 (2016).","journal-title":"Cell Rep"},{"key":"BFsrep37941_CR25","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/nri2449","volume":"8","author":"GS Hotamisligil","year":"2008","unstructured":"Hotamisligil, G. S. & Erbay, E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8, 923\u2013934 (2008).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep37941_CR26","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1210\/en.2005-0969","volume":"147","author":"H Sell","year":"2006","unstructured":"Sell, H., Dietze-Schroeder, D., Kaiser, U. & Eckel, J. Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle. Endocrinology 147, 2458\u20132467 (2006).","journal-title":"Endocrinology"},{"key":"BFsrep37941_CR27","doi-asserted-by":"publisher","first-page":"E866","DOI":"10.1152\/ajpendo.00104.2009","volume":"297","author":"T Nedachi","year":"2009","unstructured":"Nedachi, T., Hatakeyama, H., Kono, T., Sato, M. & Kanzaki, M. Characterization of contraction-inducible CXC chemokines and their roles in C2C12 myocytes. Am J Physiol Endocrinol Metab 297, E866\u2013878 (2009).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFsrep37941_CR28","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nm1185","volume":"11","author":"MC Arkan","year":"2005","unstructured":"Arkan, M. C. et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11, 191\u2013198 (2005).","journal-title":"Nat Med"},{"key":"BFsrep37941_CR29","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.immuni.2013.04.001","volume":"38","author":"JI Odegaard","year":"2013","unstructured":"Odegaard, J. I. & Chawla, A. The immune system as a sensor of the metabolic state. Immunity 38, 644\u2013654 (2013).","journal-title":"Immunity"},{"key":"BFsrep37941_CR30","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.1128\/IAI.00286-06","volume":"74","author":"JH Boyd","year":"2006","unstructured":"Boyd, J. H. et al. Toll-like receptors differentially regulate CC and CXC chemokines in skeletal muscle via NF-kappaB and calcineurin. Infect Immun 74, 6829\u20136838 (2006).","journal-title":"Infect Immun"},{"key":"BFsrep37941_CR31","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.2337\/db08-0038","volume":"57","author":"SM Reyna","year":"2008","unstructured":"Reyna, S. M. et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 57, 2595\u20132602 (2008).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1042\/CS20110357","volume":"122","author":"MR Dasu","year":"2012","unstructured":"Dasu, M. R., Ramirez, S. & Isseroff, R. R. Toll-like receptors and diabetes: a therapeutic perspective. Clin Sci (Lond) 122, 203\u2013214 (2012).","journal-title":"Clin Sci (Lond)"},{"key":"BFsrep37941_CR33","doi-asserted-by":"publisher","first-page":"e47713","DOI":"10.1371\/journal.pone.0047713","volume":"7","author":"KA Kim","year":"2012","unstructured":"Kim, K. A., Gu, W., Lee, I. A., Joh, E. H. & Kim, D. H. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7, e47713 (2012).","journal-title":"PLoS One"},{"key":"BFsrep37941_CR34","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471\u2013484 (2006).","journal-title":"Cell"},{"key":"BFsrep37941_CR35","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature05485","volume":"444","author":"GS Hotamisligil","year":"2006","unstructured":"Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860\u2013867 (2006).","journal-title":"Nature"},{"key":"BFsrep37941_CR36","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1097\/MCO.0b013e32833aabd9","volume":"13","author":"G Kewalramani","year":"2010","unstructured":"Kewalramani, G., Bilan, P. J. & Klip, A. Muscle insulin resistance: assault by lipids, cytokines and local macrophages. Curr Opin Clin Nutr Metab Care 13, 382\u2013390 (2010).","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"BFsrep37941_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj20030407","volume":"374","author":"PC Heinrich","year":"2003","unstructured":"Heinrich, P. C. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374, 1\u201320 (2003).","journal-title":"Biochem J"},{"key":"BFsrep37941_CR38","doi-asserted-by":"publisher","first-page":"13221","DOI":"10.1074\/jbc.271.22.13221","volume":"271","author":"E Caldenhoven","year":"1996","unstructured":"Caldenhoven, E. et al. STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription. J Biol Chem 271, 13221\u201313227 (1996).","journal-title":"J Biol Chem"},{"key":"BFsrep37941_CR39","doi-asserted-by":"publisher","first-page":"14111","DOI":"10.1074\/jbc.M511797200","volume":"281","author":"HH Ho","year":"2006","unstructured":"Ho, H. H. & Ivashkiv, L. B. Role of STAT3 in type I interferon responses. Negative regulation of STAT1-dependent inflammatory gene activation. J Biol Chem 281, 14111\u201314118 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep37941_CR40","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/ncb1086","volume":"6","author":"T Bouwmeester","year":"2004","unstructured":"Bouwmeester, T. et al. A physical and functional map of the human TNF-alpha\/NF-kappa B signal transduction pathway. Nat Cell Biol 6, 97\u2013105 (2004).","journal-title":"Nat Cell Biol"},{"key":"BFsrep37941_CR41","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/nm.3800","volume":"21","author":"P Li","year":"2015","unstructured":"Li, P. et al. LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes. Nat Med 21, 239\u2013247 (2015).","journal-title":"Nat Med"},{"key":"BFsrep37941_CR42","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1146\/annurev-immunol-031210-101322","volume":"29","author":"MF Gregor","year":"2011","unstructured":"Gregor, M. F. & Hotamisligil, G. S. Inflammatory mechanisms in obesity. Annu Rev Immunol 29, 415\u2013445 (2011).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep37941_CR43","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nm.2279","volume":"17","author":"B Vandanmagsar","year":"2011","unstructured":"Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17, 179\u2013188 (2011).","journal-title":"Nat Med"},{"key":"BFsrep37941_CR44","doi-asserted-by":"publisher","first-page":"35279","DOI":"10.1074\/jbc.M706762200","volume":"282","author":"MT Nguyen","year":"2007","unstructured":"Nguyen, M. T. et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 282, 35279\u201335292 (2007).","journal-title":"J Biol Chem"},{"key":"BFsrep37941_CR45","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nri1733","volume":"5","author":"S Gordon","year":"2005","unstructured":"Gordon, S. & Taylor, P. R. Monocyte and macrophage heterogeneity. Nat Rev Immunol 5, 953\u2013964 (2005).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep37941_CR46","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.2337\/db08-1475","volume":"58","author":"S Fujisaka","year":"2009","unstructured":"Fujisaka, S. et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 2574\u20132582 (2009).","journal-title":"Diabetes"},{"key":"BFsrep37941_CR47","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1182\/blood.V96.2.719","volume":"96","author":"N Faust","year":"2000","unstructured":"Faust, N., Varas, F., Kelly, L. M., Heck, S. & Graf, T. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96, 719\u2013726 (2000).","journal-title":"Blood"},{"key":"BFsrep37941_CR48","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1146\/annurev.cellbio.12.1.417","volume":"12","author":"A Weiss","year":"1996","unstructured":"Weiss, A. & Leinwand, L. A. The mammalian myosin heavy chain gene family. Annu Rev Cell Dev Biol 12, 417\u2013439 (1996).","journal-title":"Annu Rev Cell Dev Biol"},{"key":"BFsrep37941_CR49","doi-asserted-by":"publisher","first-page":"C1723","DOI":"10.1152\/ajpcell.1994.267.6.C1723","volume":"267","author":"V Smerdu","year":"1994","unstructured":"Smerdu, V., Karsch-Mizrachi, I., Campione, M., Leinwand, L. & Schiaffino, S. Type IIx myosin heavy chain transcripts are expressed in type IIb fibers of human skeletal muscle. Am J Physiol 267, C1723\u20131728 (1994).","journal-title":"Am J Physiol"},{"key":"BFsrep37941_CR50","first-page":"53","volume":"11","author":"P Plomgaard","year":"2005","unstructured":"Plomgaard, P., Penkowa, M. & Pedersen, B. K. Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles. Exerc Immunol Rev 11, 53\u201363 (2005).","journal-title":"Exerc Immunol Rev"},{"key":"BFsrep37941_CR51","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1172\/JCI200319451","volume":"112","author":"H Xu","year":"2003","unstructured":"Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 1821\u20131830 (2003).","journal-title":"J Clin Invest"},{"key":"BFsrep37941_CR52","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.4049\/jimmunol.1000021","volume":"185","author":"H Yang","year":"2010","unstructured":"Yang, H. et al. Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. J Immunol 185, 1836\u20131845 (2010).","journal-title":"J Immunol"},{"key":"BFsrep37941_CR53","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1080\/13813450903079314","volume":"115","author":"PJ Bilan","year":"2009","unstructured":"Bilan, P. J. et al. Direct and macrophage-mediated actions of fatty acids causing insulin resistance in muscle cells. Arch Physiol Biochem 115, 176\u2013190 (2009).","journal-title":"Arch Physiol Biochem"},{"key":"BFsrep37941_CR54","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/oby.20615","volume":"22","author":"LN Fink","year":"2014","unstructured":"Fink, L. N. et al. Pro-inflammatory macrophages increase in skeletal muscle of high fat-fed mice and correlate with metabolic risk markers in humans. Obesity (Silver Spring) 22, 747\u2013757 (2014).","journal-title":"Obesity (Silver Spring)"},{"key":"BFsrep37941_CR55","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1530\/JOE-13-0160","volume":"219","author":"Y Wu","year":"2013","unstructured":"Wu, Y. et al. Chronic inflammation exacerbates glucose metabolism disorders in C57BL\/6J mice fed with high-fat diet. J Endocrinol 219, 195\u2013204 (2013).","journal-title":"J Endocrinol"},{"key":"BFsrep37941_CR56","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1111\/dom.12274","volume":"16","author":"B Vandanmagsar","year":"2014","unstructured":"Vandanmagsar, B. et al. Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture. Diabetes Obes Metab 16, 728\u2013738 (2014).","journal-title":"Diabetes Obes Metab"},{"key":"BFsrep37941_CR57","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/s00125-007-0861-3","volume":"51","author":"MS Radin","year":"2008","unstructured":"Radin, M. S., Sinha, S., Bhatt, B. A., Dedousis, N. & O\u2019Doherty, R. M. Inhibition or deletion of the lipopolysaccharide receptor Toll-like receptor-4 confers partial protection against lipid-induced insulin resistance in rodent skeletal muscle. Diabetologia 51, 336\u2013346 (2008).","journal-title":"Diabetologia"},{"key":"BFsrep37941_CR58","doi-asserted-by":"publisher","first-page":"26865","DOI":"10.1074\/jbc.M513304200","volume":"281","author":"JJ Senn","year":"2006","unstructured":"Senn, J. J. Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes. J Biol Chem 281, 26865\u201326875 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep37941_CR59","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1002\/eji.201141783","volume":"41","author":"LB Ivashkiv","year":"2011","unstructured":"Ivashkiv, L. B. Inflammatory signaling in macrophages: transitions from acute to tolerant and alternative activation states. Eur J Immunol 41, 2477\u20132481 (2011).","journal-title":"Eur J Immunol"},{"key":"BFsrep37941_CR60","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrendo.2012.49","volume":"8","author":"BK Pedersen","year":"2012","unstructured":"Pedersen, B. K. & Febbraio, M. A. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8, 457\u2013465 (2012).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep37941_CR61","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/bs.pmbts.2015.07.003","volume":"135","author":"J Allen","year":"2015","unstructured":"Allen, J., Sun, Y. & Woods, J. A. Exercise and the Regulation of Inflammatory Responses. Prog Mol Biol Transl Sci 135, 337\u2013354 (2015).","journal-title":"Prog Mol Biol Transl Sci"},{"key":"BFsrep37941_CR62","first-page":"18","volume":"7","author":"BK Pedersen","year":"2001","unstructured":"Pedersen, B. K. et al. Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 7, 18\u201331 (2001).","journal-title":"Exerc Immunol Rev"},{"key":"BFsrep37941_CR63","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1249\/MSS.0b013e31822f94ac","volume":"44","author":"BK Pedersen","year":"2012","unstructured":"Pedersen, B. K. Muscular interleukin-6 and its role as an energy sensor. Med Sci Sports Exerc 44, 392\u2013396 (2012).","journal-title":"Med Sci Sports Exerc"},{"key":"BFsrep37941_CR64","doi-asserted-by":"crossref","unstructured":"Wang, W. F. et al. Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats. Endocrine (2014).","DOI":"10.1007\/s12020-014-0433-5"},{"key":"BFsrep37941_CR65","doi-asserted-by":"publisher","first-page":"e82275","DOI":"10.1371\/journal.pone.0082275","volume":"8","author":"C Zhang","year":"2013","unstructured":"Zhang, C. et al. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation. PLoS One 8, e82275 (2013).","journal-title":"PLoS One"},{"key":"BFsrep37941_CR66","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1126\/science.1230721","volume":"339","author":"JI Odegaard","year":"2013","unstructured":"Odegaard, J. I. & Chawla, A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science 339, 172\u2013177 (2013).","journal-title":"Science"},{"key":"BFsrep37941_CR67","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nature11862","volume":"493","author":"LA O\u2019Neill","year":"2013","unstructured":"O\u2019Neill, L. A. & Hardie, D. G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346\u2013355 (2013).","journal-title":"Nature"},{"key":"BFsrep37941_CR68","doi-asserted-by":"publisher","first-page":"E1009","DOI":"10.1152\/ajpendo.90558.2008","volume":"295","author":"JE Galgani","year":"2008","unstructured":"Galgani, J. E., Moro, C. & Ravussin, E. Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab 295, E1009\u20131017 (2008).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFsrep37941_CR69","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.cmet.2012.04.010","volume":"15","author":"DM Muoio","year":"2012","unstructured":"Muoio, D. M. & Neufer, P. D. Lipid-induced mitochondrial stress and insulin action in muscle. Cell Metab 15, 595\u2013605 (2012).","journal-title":"Cell Metab"},{"key":"BFsrep37941_CR70","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1210\/me.2014-1275","volume":"29","author":"JS Burrill","year":"2015","unstructured":"Burrill, J. S. et al. Inflammation and ER stress regulate branched-chain amino acid uptake and metabolism in adipocytes. Mol Endocrinol 29, 411\u2013420 (2015).","journal-title":"Mol Endocrinol"},{"key":"BFsrep37941_CR71","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1111\/dom.12248","volume":"16","author":"KR Haynie","year":"2014","unstructured":"Haynie, K. R., Vandanmagsar, B., Wicks, S. E., Zhang, J. & Mynatt, R. L. Inhibition of carnitine palymitoyltransferase1b induces cardiac hypertrophy and mortality in mice. Diabetes Obes Metab 16, 757\u2013760 (2014).","journal-title":"Diabetes Obes Metab"},{"key":"BFsrep37941_CR72","doi-asserted-by":"publisher","first-page":"16917","DOI":"10.1038\/srep16917","volume":"5","author":"JM Salbaum","year":"2015","unstructured":"Salbaum, J. M. et al. Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain. Sci Rep 5, 16917 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep37941_CR73","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102, 15545\u201315550 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep37941_CR74","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","volume":"27","author":"H Ogata","year":"1999","unstructured":"Ogata, H. et al. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 27, 29\u201334 (1999).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep37941_CR75","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1093\/bioinformatics\/btf877","volume":"19","author":"A Reiner","year":"2003","unstructured":"Reiner, A., Yekutieli, D. & Benjamini, Y. Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics 19, 368\u2013375 (2003).","journal-title":"Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep37941.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37941","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37941.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T20:13:37Z","timestamp":1672863217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep37941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,28]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep37941"],"URL":"https:\/\/doi.org\/10.1038\/srep37941","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,28]]},"assertion":[{"value":"27 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37941"}}