{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:29:15Z","timestamp":1790173755655,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T00:00:00Z","timestamp":1439251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T00:00:00Z","timestamp":1439251200000},"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><jats:p>Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or <jats:italic>in vitro<\/jats:italic> adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the \u201cbrowning\u201d effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes.<\/jats:p>","DOI":"10.1038\/srep13091","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T10:38:40Z","timestamp":1439289520000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Glutathione Decrement Drives Thermogenic Program In Adipose Cells"],"prefix":"10.1038","volume":"5","author":[{"given":"Daniele","family":"Lettieri Barbato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tatulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Maria Cannata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Aquilano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Ciriolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,11]]},"reference":[{"key":"BFsrep13091_CR1","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.bbalip.2014.08.004","volume":"1841","author":"D Lettieri Barbato","year":"2014","unstructured":"Lettieri Barbato, D., Aquilano, K. & Ciriolo, M. R. FoxO1 at the nexus between fat catabolism and longevity pathways. Biochim Biophys Acta 1841, 1555\u20131560 (2014).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bbadis.2013.05.011","volume":"1842","author":"YH Lee","year":"2014","unstructured":"Lee, Y. H., Mottillo, E. P. & Granneman, J. G. Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 1842, 358\u2013369 (2014).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/cdd.2013.137","volume":"21","author":"D Lettieri Barbato","year":"2014","unstructured":"Lettieri Barbato, D. et al. Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation. Cell Death Differ 21, 113\u2013123 (2014).","journal-title":"Cell Death Differ"},{"key":"BFsrep13091_CR4","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1172\/JCI3155","volume":"102","author":"C Guerra","year":"1998","unstructured":"Guerra, C., Koza, R. A., Yamashita, H., Walsh, K. & Kozak, L. P. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 102, 412\u2013420 (1998).","journal-title":"J Clin Invest"},{"key":"BFsrep13091_CR5","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.1186034","volume":"328","author":"A Vegiopoulos","year":"2010","unstructured":"Vegiopoulos, A. et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328, 1158\u20131161 (2010).","journal-title":"Science"},{"key":"BFsrep13091_CR6","doi-asserted-by":"crossref","first-page":"7153","DOI":"10.1074\/jbc.M109.053942","volume":"285","author":"N Petrovic","year":"2010","unstructured":"Petrovic, N. et al. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285, 7153\u20137164 (2010).","journal-title":"J Biol Chem"},{"key":"BFsrep13091_CR7","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1126\/science.1190816","volume":"328","author":"J Ishibashi","year":"2010","unstructured":"Ishibashi, J. & Seale, P. Medicine. Beige can be slimming. Science 328, 1113\u20131114 (2010).","journal-title":"Science"},{"key":"BFsrep13091_CR8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1101\/gad.177857.111","volume":"26","author":"FM Fisher","year":"2012","unstructured":"Fisher, F. M. et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26, 271\u2013281 (2012).","journal-title":"Genes Dev"},{"key":"BFsrep13091_CR9","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","volume":"481","author":"P Bostrom","year":"2012","unstructured":"Bostrom, P. et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463\u2013468 (2012).","journal-title":"Nature"},{"key":"BFsrep13091_CR10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cmet.2011.06.020","volume":"14","author":"L Cao","year":"2011","unstructured":"Cao, L. et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab 14, 324\u2013338 (2011).","journal-title":"Cell Metab"},{"key":"BFsrep13091_CR11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/febs.12619","volume":"281","author":"F Norheim","year":"2014","unstructured":"Norheim, F. et al. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 281, 739\u2013749 (2014).","journal-title":"FEBS J"},{"key":"BFsrep13091_CR12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrendo.2013.204","volume":"10","author":"A Bartelt","year":"2014","unstructured":"Bartelt, A. & Heeren, J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10, 24\u201336 (2014).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep13091_CR13","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.bbalip.2013.02.005","volume":"1831","author":"A Frontini","year":"2013","unstructured":"Frontini, A. et al. White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 1831, 950\u2013959 (2013).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR14","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cmet.2014.06.011","volume":"20","author":"M Petruzzelli","year":"2014","unstructured":"Petruzzelli, M. et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab 20, 433\u2013447 (2014).","journal-title":"Cell Metab"},{"key":"BFsrep13091_CR15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature13528","volume":"513","author":"S Kir","year":"2014","unstructured":"Kir, S. et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 513, 100\u2013104 (2014).","journal-title":"Nature"},{"key":"BFsrep13091_CR16","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa0810780","volume":"360","author":"AM Cypess","year":"2009","unstructured":"Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360, 1509\u20131517 (2009).","journal-title":"N Engl J Med"},{"key":"BFsrep13091_CR17","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.2337\/db12-1430","volume":"62","author":"H Sacks","year":"2013","unstructured":"Sacks, H. & Symonds, M. E. Anatomical locations of human brown adipose tissue: functional relevance and implications in obesity and type 2 diabetes. Diabetes 62, 1783\u20131790 (2013).","journal-title":"Diabetes"},{"key":"BFsrep13091_CR18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.bbalip.2013.02.003","volume":"1831","author":"P Flachs","year":"2013","unstructured":"Flachs, P., Rossmeisl, M., Kuda, O. & Kopecky, J. Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: a key to lean phenotype. Biochim Biophys Acta 1831, 986\u20131003 (2013).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR19","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3390\/cells1040976","volume":"1","author":"GS Liu","year":"2012","unstructured":"Liu, G. S., Chan, E. C., Higuchi, M., Dusting, G. J. & Jiang, F. Redox mechanisms in regulation of adipocyte differentiation: beyond a general stress response. Cells 1, 976\u2013993 (2012).","journal-title":"Cells"},{"key":"BFsrep13091_CR20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3945\/an.112.003103","volume":"4","author":"KS Schneider","year":"2013","unstructured":"Schneider, K. S. & Chan, J. Y. Emerging role of Nrf2 in adipocytes and adipose biology. Adv Nutr 4, 62\u201366 (2013).","journal-title":"Adv Nutr"},{"key":"BFsrep13091_CR21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1096\/fj.11-189639","volume":"26","author":"RJ Mailloux","year":"2012","unstructured":"Mailloux, R. J., Adjeitey, C. N., Xuan, J. Y. & Harper, M. E. Crucial yet divergent roles of mitochondrial redox state in skeletal muscle vs. brown adipose tissue energetics. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 26, 363\u2013375 (2012).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"BFsrep13091_CR22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bbabio.2009.11.005","volume":"1797","author":"BG Hill","year":"2010","unstructured":"Hill, B. G., Higdon, A. N., Dranka, B. P. & Darley-Usmar, V. M. Regulation of vascular smooth muscle cell bioenergetic function by protein glutathiolation. Biochim Biophys Acta 1797, 285\u2013295 (2010).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR23","doi-asserted-by":"crossref","first-page":"39646","DOI":"10.1074\/jbc.M110.164160","volume":"285","author":"J Garcia","year":"2010","unstructured":"Garcia, J. et al. Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J Biol Chem 285, 39646\u201339654 (2010).","journal-title":"J Biol Chem"},{"key":"BFsrep13091_CR24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3389\/fphar.2014.00196","volume":"5","author":"K Aquilano","year":"2014","unstructured":"Aquilano, K., Baldelli, S. & Ciriolo, M. R. Glutathione: new roles in redox signaling for an old antioxidant. Front Pharmacol 5, 196 (2014).","journal-title":"Front Pharmacol"},{"key":"BFsrep13091_CR25","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/biof.5520170130","volume":"17","author":"WH Watson","year":"2003","unstructured":"Watson, W. H., Chen, Y. & Jones, D. P. Redox state of glutathione and thioredoxin in differentiation and apoptosis. Biofactors 17, 307\u2013314 (2003).","journal-title":"Biofactors"},{"key":"BFsrep13091_CR26","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1016\/j.febslet.2006.10.052","volume":"580","author":"A Galinier","year":"2006","unstructured":"Galinier, A. et al. Site specific changes of redox metabolism in adipose tissue of obese Zucker rats. FEBS Lett 580, 6391\u20136398 (2006).","journal-title":"FEBS Lett"},{"key":"BFsrep13091_CR27","doi-asserted-by":"crossref","first-page":"12682","DOI":"10.1074\/jbc.M506949200","volume":"281","author":"A Galinier","year":"2006","unstructured":"Galinier, A. et al. Adipose tissue proadipogenic redox changes in obesity. The Journal of biological chemistry 281, 12682\u201312687 (2006).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep13091_CR28","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1002\/jcp.22542","volume":"226","author":"P Vigilanza","year":"2011","unstructured":"Vigilanza, P., Aquilano, K., Baldelli, S., Rotilio, G. & Ciriolo, M. R. Modulation of intracellular glutathione affects adipogenesis in 3T3-L1 cells. Journal of cellular physiology 226, 2016\u20132024 (2011).","journal-title":"Journal of cellular physiology"},{"key":"BFsrep13091_CR29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.diff.2010.04.005","volume":"80","author":"BR Imhoff","year":"2010","unstructured":"Imhoff, B. R. & Hansen, J. M. Extracellular redox environments regulate adipocyte differentiation. Differentiation; research in biological diversity 80, 31\u201339 (2010).","journal-title":"Differentiation; research in biological diversity"},{"key":"BFsrep13091_CR30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2478\/s11658-010-0042-0","volume":"16","author":"BR Imhoff","year":"2011","unstructured":"Imhoff, B. R. & Hansen, J. M. Differential redox potential profiles during adipogenesis and osteogenesis. Cell Mol Biol Lett 16, 149\u2013161 (2011).","journal-title":"Cell Mol Biol Lett"},{"key":"BFsrep13091_CR31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1152\/jappl.1988.64.1.115","volume":"64","author":"K Gohil","year":"1988","unstructured":"Gohil, K., Viguie, C., Stanley, W. C., Brooks, G. A. & Packer, L. Blood glutathione oxidation during human exercise. J Appl Physiol (1985) 64, 115\u2013119 (1988).","journal-title":"J Appl Physiol (1985)"},{"key":"BFsrep13091_CR32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0891-5849(92)90180-O","volume":"13","author":"G Barja de Quiroga","year":"1992","unstructured":"Barja de Quiroga, G. Brown fat thermogenesis and exercise: two examples of physiological oxidative stress? Free radical biology & medicine 13, 325\u2013340 (1992).","journal-title":"Free radical biology & medicine"},{"key":"BFsrep13091_CR33","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/S0891-5849(99)00145-8","volume":"27","author":"WG Kirlin","year":"1999","unstructured":"Kirlin, W. G. et al. Glutathione redox potential in response to differentiation and enzyme inducers. Free Radic Biol Med 27, 1208\u20131218 (1999).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep13091_CR34","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0891-5849(01)00480-4","volume":"30","author":"FQ Schafer","year":"2001","unstructured":"Schafer, F. Q. & Buettner, G. R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide\/glutathione couple. Free Radic Biol Med 30, 1191\u20131212 (2001).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep13091_CR35","doi-asserted-by":"crossref","first-page":"24660","DOI":"10.1074\/jbc.M703101200","volume":"282","author":"G Karamanlidis","year":"2007","unstructured":"Karamanlidis, G., Karamitri, A., Docherty, K., Hazlerigg, D. G. & Lomax, M. A. C\/EBPbeta reprograms white 3T3-L1 preadipocytes to a Brown adipocyte pattern of gene expression. J Biol Chem 282, 24660\u201324669 (2007).","journal-title":"J Biol Chem"},{"key":"BFsrep13091_CR36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.diff.2014.07.002","volume":"87","author":"S Rajan","year":"2014","unstructured":"Rajan, S. et al. Adipocyte transdifferentiation and its molecular targets. Differentiation 87, 183\u2013192 (2014).","journal-title":"Differentiation"},{"key":"BFsrep13091_CR37","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.bbalip.2013.01.015","volume":"1831","author":"D Barneda","year":"2013","unstructured":"Barneda, D., Frontini, A., Cinti, S. & Christian, M. Dynamic changes in lipid droplet-associated proteins in the \u201cbrowning\u201d of white adipose tissues. Biochim Biophys Acta 1831, 924\u2013933 (2013).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep13091_CR38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1292\/jvms.13-0359","volume":"76","author":"H Asano","year":"2014","unstructured":"Asano, H. et al. Induction of beige-like adipocytes in 3T3-L1 cells. J Vet Med Sci 76, 57\u201364 (2014).","journal-title":"J Vet Med Sci"},{"key":"BFsrep13091_CR39","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.cmet.2012.02.001","volume":"15","author":"A Ortega-Molina","year":"2012","unstructured":"Ortega-Molina, A. et al. Pten positively regulates brown adipose function, energy expenditure and longevity. Cell Metab 15, 382\u2013394 (2012).","journal-title":"Cell Metab"},{"key":"BFsrep13091_CR40","doi-asserted-by":"crossref","first-page":"e861","DOI":"10.1038\/cddis.2013.404","volume":"4","author":"D Lettieri Barbato","year":"2013","unstructured":"Lettieri Barbato, D., Tatulli, G., Aquilano, K. & Ciriolo, M. R. FoxO1 controls lysosomal acid lipase in adipocytes: implication of lipophagy during nutrient restriction and metformin treatment. Cell death & disease 4, e861 (2013).","journal-title":"Cell death & disease"},{"key":"BFsrep13091_CR41","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.freeradbiomed.2008.01.007","volume":"44","author":"V Cattan","year":"2008","unstructured":"Cattan, V. et al. Chronic oxidative stress induces a tissue-specific reduction in telomere length in CAST\/Ei mice. Free Radic Biol Med 44, 1592\u20131598 (2008).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep13091_CR42","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1006\/abbi.1995.1125","volume":"316","author":"C Leeuwenburgh","year":"1995","unstructured":"Leeuwenburgh, C. & Ji, L. L. Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. Arch Biochem Biophys 316, 941\u2013949 (1995).","journal-title":"Arch Biochem Biophys"},{"key":"BFsrep13091_CR43","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1007\/s00125-004-1391-x","volume":"47","author":"T Ogihara","year":"2004","unstructured":"Ogihara, T. et al. Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. Diabetologia 47, 794\u2013805 (2004).","journal-title":"Diabetologia"},{"key":"BFsrep13091_CR44","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1038\/oby.2011.298","volume":"19","author":"HM Findeisen","year":"2011","unstructured":"Findeisen, H. M. et al. Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity. Obesity 19, 2429\u20132432 (2011).","journal-title":"Obesity"},{"key":"BFsrep13091_CR45","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.taap.2011.09.017","volume":"257","author":"EL Kendig","year":"2011","unstructured":"Kendig, E. L. et al. Lipid metabolism and body composition in Gclm(-\/-) mice. Toxicology and applied pharmacology 257, 338\u2013348 (2011).","journal-title":"Toxicology and applied pharmacology"},{"key":"BFsrep13091_CR46","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/obr.12116","volume":"15","author":"K Chechi","year":"2014","unstructured":"Chechi, K., Nedergaard, J. & Richard, D. Brown adipose tissue as an anti-obesity tissue in humans. Obes Rev 15, 92\u2013106 (2014).","journal-title":"Obes Rev"},{"key":"BFsrep13091_CR47","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.cmet.2011.08.010","volume":"14","author":"D Sellayah","year":"2011","unstructured":"Sellayah, D., Bharaj, P. & Sikder, D. Orexin is required for brown adipose tissue development, differentiation and function. Cell Metab 14, 478\u2013490 (2011).","journal-title":"Cell Metab"},{"key":"BFsrep13091_CR48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/nyas.12276","volume":"1302","author":"D Sellayah","year":"2013","unstructured":"Sellayah, D. & Sikder, D. Feeding the heat on brown fat. Ann N Y Acad Sci 1302, 11\u201323 (2013).","journal-title":"Ann N Y Acad Sci"},{"key":"BFsrep13091_CR49","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmet.2013.08.005","volume":"18","author":"G Gaich","year":"2013","unstructured":"Gaich, G. et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18, 333\u2013340 (2013).","journal-title":"Cell Metab"},{"key":"BFsrep13091_CR50","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1753-0407.2012.00194.x","volume":"4","author":"F Sanchis-Gomar","year":"2012","unstructured":"Sanchis-Gomar, F., Lippi, G., Mayero, S., Perez-Quilis, C. & Garcia-Gimenez, J. L. Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes 4, 196 (2012).","journal-title":"J Diabetes"},{"key":"BFsrep13091_CR51","doi-asserted-by":"crossref","first-page":"e73680","DOI":"10.1371\/journal.pone.0073680","volume":"8","author":"S Raschke","year":"2013","unstructured":"Raschke, S. et al. Evidence against a beneficial effect of irisin in humans. PLoS One 8, e73680 (2013).","journal-title":"PLoS One"},{"key":"BFsrep13091_CR52","doi-asserted-by":"crossref","unstructured":"Crujeiras, A. B., Pardo, M. & Casanueva, F. F. Irisin: \u2018fat\u2019 or artefact. Clin Endocrinol (Oxf) (2014) 10.1111\/cen.12627.","DOI":"10.1111\/cen.12627"},{"key":"BFsrep13091_CR53","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1530\/JOE-14-0189","volume":"222","author":"M Elsen","year":"2014","unstructured":"Elsen, M., Raschke, S. & Eckel, J. Browning of white fat: does irisin play a role in humans? J Endocrinol 222, R25\u201338 (2014).","journal-title":"J Endocrinol"},{"key":"BFsrep13091_CR54","doi-asserted-by":"crossref","first-page":"12480","DOI":"10.1073\/pnas.1310261110","volume":"110","author":"L Ye","year":"2013","unstructured":"Ye, L. et al. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci USA 110, 12480\u201312485 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep13091_CR55","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1093\/jnci\/89.23.1789","volume":"89","author":"HH Bailey","year":"1997","unstructured":"Bailey, H. H. et al. Phase I study of continuous-infusion L-S,R-buthionine sulfoximine with intravenous melphalan. J Natl Cancer Inst 89, 1789\u20131796 (1997).","journal-title":"J Natl Cancer Inst"},{"key":"BFsrep13091_CR56","first-page":"55s","volume":"81 Suppl 2","author":"SE Bates","year":"1994","unstructured":"Bates, S. E. et al. Chemoresistance in the clinic: overview 1994. Bull Cancer 81 Suppl 2, 55s\u201361s (1994).","journal-title":"Bull Cancer"},{"key":"BFsrep13091_CR57","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2337\/db07-0698","volume":"57","author":"J Nakae","year":"2008","unstructured":"Nakae, J. et al. Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure. Diabetes 57, 563\u2013576 (2008).","journal-title":"Diabetes"},{"key":"BFsrep13091_CR58","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/nprot.2009.151","volume":"4","author":"MR Wieckowski","year":"2009","unstructured":"Wieckowski, M. R., Giorgi, C., Lebiedzinska, M., Duszynski, J. & Pinton, P. Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells. Nat Protoc 4, 1582\u20131590 (2009).","journal-title":"Nat Protoc"},{"key":"BFsrep13091_CR59","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jneumeth.2005.08.018","volume":"152","author":"T Kristian","year":"2006","unstructured":"Kristian, T., Hopkins, I. B., McKenna, M. C. & Fiskum, G. Isolation of mitochondria with high respiratory control from primary cultures of neurons and astrocytes using nitrogen cavitation. J Neurosci Methods 152, 136\u2013143 (2006).","journal-title":"J Neurosci Methods"},{"key":"BFsrep13091_CR60","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.biocel.2010.10.016","volume":"43","author":"S Baldelli","year":"2011","unstructured":"Baldelli, S., Aquilano, K., Rotilio, G. & Ciriolo, M. R. Neuronal nitric oxide synthase interacts with Sp1 through the PDZ domain inhibiting Sp1-mediated copper-zinc superoxide dismutase expression. Int J Biochem Cell Biol 43, 163\u2013169 (2011).","journal-title":"Int J Biochem Cell Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep13091","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep13091.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep13091.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T23:38:37Z","timestamp":1672961917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep13091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,11]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,10,16]]}},"alternative-id":["BFsrep13091"],"URL":"https:\/\/doi.org\/10.1038\/srep13091","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,11]]},"assertion":[{"value":"29 January 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2015","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The version of this Article previously published incorrectly indicated that Daniele Lettieri Barbato and Giuseppe Tatulli jointly supervised the work, rather than Katia Aquilano and Maria R. Ciriolo. In addition, Daniele Lettieri Barbato and Giuseppe Tatulli were not listed as equally contributing authors. These errors have now been corrected in both the PDF and HTML version of the paper.","order":6,"name":"change_details","label":"Change Details","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":"13091"}}