Golozoubova, V. et al. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. FASEB J. 15, 2048–2050 (2001).
Nedergaard, J. et al. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim. Biophys. Acta 1504, 82–106 (2001).
Kajimura, S., Spiegelman, B.M. & Seale, P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab. 22, 546–559 (2015).
Wu, J. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012).
Shabalina, I.G. et al. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 5, 1196–1203 (2013).
Okamatsu-Ogura, Y. et al. Thermogenic ability of uncoupling protein 1 in beige adipocytes in mice. PLoS One 8, e84229 (2013).
Cinti, S. The Adipose Organ (Editrice Kurtis, 1999).
Petrovic, N. et al. Chronic peroxisome proliferator-activated receptor γ (PPARγ) 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, 7153–7164 (2010).
Nedergaard, J. & Cannon, B. UCP1 mRNA does not produce heat. Biochim. Biophys. Acta 1831, 943–949 (2013).
Xue, B. et al. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J. Lipid Res. 48, 41–51 (2007).
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, 412–420 (1998).
Seale, P. et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J. Clin. Invest. 121, 96–105 (2011).
Shinoda, K. et al. Phosphoproteomics identifies CK2 as a negative regulator of beige adipocyte thermogenesis and energy expenditure. Cell Metab. 22, 997–1008 (2015).
McDonald, M.E. et al. Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes. Cell 160, 105–118 (2015).
Vegiopoulos, A. et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328, 1158–1161 (2010).
Cohen, P. et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156, 304–316 (2014).
Ohno, H., Shinoda, K., Ohyama, K., Sharp, L.Z. & Kajimura, S. EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 504, 163–167 (2013).
Ukropec, J., Anunciado, R.P., Ravussin, Y., Hulver, M.W. & Kozak, L.P. UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1−/− mice. J. Biol. Chem. 281, 31894–31908 (2006).
Granneman, J.G., Burnazi, M., Zhu, Z. & Schwamb, L.A. White adipose tissue contributes to UCP1-independent thermogenesis. Am. J. Physiol. Endocrinol. Metab. 285, E1230–E1236 (2003).
Rowland, L.A., Bal, N.C., Kozak, L.P. & Periasamy, M. Uncoupling protein 1 and sarcolipin are required to maintain optimal thermogenesis, and loss of both systems compromises survival of mice under cold stress. J. Biol. Chem. 290, 12282–12289 (2015).
Bal, N.C. et al. Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat. Med. 18, 1575–1579 (2012).
Kazak, L. et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 163, 643–655 (2015).
Enerbäck, S. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997).
Tripathi, S. et al. Meta- and orthogonal integration of influenza “OMICs” data defines a role for UBR4 in virus budding. Cell Host Microbe 18, 723–735 (2015).
Fujii, J. et al. Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253, 448–451 (1991).
Quane, K.A. et al. Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat. Genet. 5, 51–55 (1993).
Shinoda, K. et al. Genetic and functional characterization of clonally derived adult human brown adipocytes. Nat. Med. 21, 389–394 (2015).
Collins, S. β-adrenoceptor signaling networks in adipocytes for recruiting stored fat and energy expenditure. Front. Endocrinol. (Lausanne) 2, 102 (2012).
Fedorenko, A., Lishko, P.V. & Kirichok, Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151, 400–413 (2012).
Bertholet, A.M. et al. Mitochondrial patch clamp of beige adipocytes reveals UCP1-positive and UCP1-negative cells both exhibiting futile creatine cycling. Cell Metab. 25, 811–822 (2017).
Lee, S.C., Nuccitelli, R. & Pappone, P.A. Adrenergically activated Ca2+ increases in brown fat cells: effects of Ca2+, K+, and K channel block. Am. J. Physiol. 264, C217–C228 (1993).
Prestle, J. et al. Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor–mediated Ca2+ leak from the sarcoplasmic reticulum and increases contractility. Circ. Res. 88, 188–194 (2001).
Gómez, A.M. et al. FKBP12.6 overexpression decreases Ca2+ spark amplitude but enhances [Ca2+]i transient in rat cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 287, H1987–H1993 (2004).
Loughrey, C.M. et al. Over-expression of FK506-binding protein FKBP12.6 alters excitation–contraction coupling in adult rabbit cardiomyocytes. J. Physiol. (Lond.) 556, 919–934 (2004).
Wehrens, X.H. et al. Protection from cardiac arrhythmia through ryanodine receptor–stabilizing protein calstabin2. Science 304, 292–296 (2004).
Santulli, G. et al. Calcium release channel RyR2 regulates insulin release and glucose homeostasis. J. Clin. Invest. 125, 1968–1978 (2015).
Berg, F., Gustafson, U. & Andersson, L. The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets. PLoS Genet. 2, e129 (2006).
Denton, R.M. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787, 1309–1316 (2009).
Marx, S.O. et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101, 365–376 (2000).
Kramarova, T.V. et al. Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c-Fo subunit P1 isoform. FASEB J. 22, 55–63 (2008).
Block, B.A. Thermogenesis in muscle. Annu. Rev. Physiol. 56, 535–577 (1994).
Fu, S. et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473, 528–531 (2011).
Park, S.W., Zhou, Y., Lee, J., Lee, J. & Ozcan, U. Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity. Proc. Natl. Acad. Sci. USA 107, 19320–19325 (2010).
Tubbs, E. et al. Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance. Diabetes 63, 3279–3294 (2014).
Arruda, A.P. et al. Chronic enrichment of hepatic endoplasmic reticulum–mitochondria contact leads to mitochondrial dysfunction in obesity. Nat. Med. 20, 1427–1435 (2014).
Yoneshiro, T. et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 19, 1755–1760 (2011).
Saito, M. et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58, 1526–1531 (2009).
Tiso, N. et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum. Mol. Genet. 10, 189–194 (2001).
Marks, A.R., Priori, S., Memmi, M., Kontula, K. & Laitinen, P.J. Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. J. Cell. Physiol. 190, 1–6 (2002).
Seale, P. et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 6, 38–54 (2007).
Feketa, V.V., Balasubramanian, A., Flores, C.M., Player, M.R. & Marrelli, S.P. Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R1040–R1050 (2013).
Soga, T. et al. Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. J. Biol. Chem. 281, 16768–16776 (2006).
Soga, T. et al. Metabolomic profiling of anionic metabolites by capillary electrophoresis mass spectrometry. Anal. Chem. 81, 6165–6174 (2009).
Soga, T. & Heiger, D.N. Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal. Chem. 72, 1236–1241 (2000).