Fighting obesity: When muscle meets fat

References

• Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol 2013; 9:13-27; PMID:23165161; http://dx.doi.org/10.1038/nrendo.2012.199
   PubMed Web of Science ®Google Scholar
• Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the third national health and nutrition examination survey, 1988-1994. Arch Intern Med 2003; 163:427-36; PMID:12588201; http://dx.doi.org/10.1001/archinte.163.4.427
   PubMed Web of Science ®Google Scholar
• Adams KF, Schatzkin A, Harris TB, Kipnis V, Mouw T, Ballard-Barbash R, Hollenbeck A, Leitzmann MF. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. New Eng J Med 2006; 355:763-78; PMID:16926275; http://dx.doi.org/10.1056/NEJMoa055643
   PubMed Web of Science ®Google Scholar
• Kabakov E, Norymberg C, Osher E, Koffler M, Tordjman K, Greenman Y, Stern N. Prevalence of hypertension in type 2 diabetes mellitus: impact of the tightening definition of high blood pressure and association with confounding risk factors. J Cardiometabolic Syndrome 2006; 1:95-101; PMID:17679829; http://dx.doi.org/10.1111/j.1559-4564.2006.05513.x
   PubMedGoogle Scholar
• Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012; 8:457-65; PMID:22473333; http://dx.doi.org/10.1038/nrendo.2012.49
   PubMed Web of Science ®Google Scholar
• Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, et al. PRDM16 controls a brown fatskeletal muscle switch. Nature 2008; 454:961-7; PMID:18719582; http://dx.doi.org/10.1038/nature07182
   PubMed Web of Science ®Google Scholar
• Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE, Giorgadze N, Tchkonia T, et al. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Nat Acad Sci U S A 2011; 108:143-8; PMID:21173238; http://dx.doi.org/10.1073/pnas.1010929108
   PubMed Web of Science ®Google Scholar
• Cinti S. The adipose organ. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2005; 73:9-15; PMID:15936182; http://dx.doi.org/10.1016/j.plefa.2005.04.010
   PubMed Web of Science ®Google Scholar
• Cinti S. The adipose organ at a glance. Dis Model Mech 2012; 5:588-94; PMID:22915020; http://dx.doi.org/10.1242/dmm.009662
   PubMed Web of Science ®Google Scholar
• Rosen Evan D, Spiegelman Bruce M. What we talk about when we talk about fat. Cell 2014; 156:20-44; PMID:24439368; http://dx.doi.org/10.1016/j.cell.2013.12.012
   PubMedGoogle Scholar
• Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, et al. Evidence for two types of brown adipose tissue in humans. Nat Med 2013; 19:631-4; PMID:23603813; http://dx.doi.org/10.1038/nm.3017
   PubMed Web of Science ®Google Scholar
• Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84:277-359; PMID:14715917; http://dx.doi.org/10.1152/physrev.00015.2003
   PubMed Web of Science ®Google Scholar
• Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 2012; 151:400-13; PMID:23063128; http://dx.doi.org/10.1016/j.cell.2012.09.010
   PubMed Web of Science ®Google Scholar
• Saito M. Brown adipose tissue as a therapeutic target for human obesity. Obes Res Clin Prac 2013; 7:e432-8; PMID:24459687; http://dx.doi.org/10.1016/j.orcp.2013.09.001
   PubMedGoogle Scholar
• Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM. White fat progenitor cells reside in the adipose vasculature. Science 2008; 322:583-6; PMID:18801968; http://dx.doi.org/10.1126/science.1156232
   PubMed Web of Science ®Google Scholar
• Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ, Cohen P, Frontini A, Bhowmick DC, Ye L, Cinti S, et al. Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Met 2012; 15:230-9; PMID:22326224; http://dx.doi.org/10.1016/j.cmet.2012.01.010
   PubMed Web of Science ®Google Scholar
• Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A, et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Met 2012; 15:222-9; PMID:22326223; http://dx.doi.org/10.1016/j.cmet.2012.01.008
   PubMed Web of Science ®Google Scholar
• Berry R, Rodeheffer MS. Characterization of the adipocyte cellular lineage in vivo. Nat Cell Biol 2013; 15:302-8; PMID:23434825; http://dx.doi.org/10.1038/ncb2696
   PubMed Web of Science ®Google Scholar
• Liu W, Liu Y, Lai X, Kuang S. Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles. Dev Biol 2012; 361:27-38; PMID:22037676; http://dx.doi.org/10.1016/j.ydbio.2011.10.011
   PubMedGoogle Scholar
• Lepper C, Fan CM. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis 2010; 48:424-36; PMID:20641127; http://dx.doi.org/10.1002/dvg.20630
   PubMed Web of Science ®Google Scholar
• Forner F, Kumar C, Luber CA, Fromme T, Klingenspor M, Mann M. Proteome differences between brown and white fat mitochondria reveal specialized metabolic functions. Cell Met 2009; 10:324-35; PMID:19808025; http://dx.doi.org/10.1016/j.cmet.2009.08.014
   PubMed Web of Science ®Google Scholar
• Schonfeld P, Wojtczak L. Brown adipose tissue mitochondria oxidizing fatty acids generate high levels of reactive oxygen species irrespective of the uncoupling protein-1 activity state. Biochimica et Biophysica Acta 2012; 1817:410-8; PMID:22226918; http://dx.doi.org/10.1016/j.bbabio.2011.12.009
   PubMedGoogle Scholar
• Rolfe DF, Brand MD. Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate. Am J Physiol 1996; 271:C1380-9; PMID:8897845
   PubMed Web of Science ®Google Scholar
• Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Nat Acad Sci U S A 2007; 104:4401-6; PMID:17360536; http://dx.doi.org/10.1073/pnas.0610615104
   PubMed Web of Science ®Google Scholar
• Yin H, Pasut A, Soleimani VD, Bentzinger CF, Antoun G, Thorn S, Seale P, Fernando P, van Ijcken W, Grosveld F, et al. MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16. Cell Met 2013; 17:210-24; PMID:23395168; http://dx.doi.org/10.1016/j.cmet.2013.01.004
   PubMed Web of Science ®Google Scholar
• Harms MJ, Ishibashi J, Wang W, Lim HW, Goyama S, Sato T, Kurokawa M, Won KJ, Seale P. Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Met 2014; 19:593-604; PMID:24703692; http://dx.doi.org/10.1016/j.cmet.2014.03.007
   PubMed Web of Science ®Google Scholar
• Shabalina IG, Petrovic N, de Jong JM, Kalinovich AV, Cannon B, Nedergaard J. UCP1 in britebeige adipose tissue mitochondria is functionally thermogenic. Cell Rep 2013; 5:1196-203; PMID:24290753; http://dx.doi.org/10.1016/j.celrep.2013.10.044
   PubMed Web of Science ®Google Scholar
• Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, et al. Identification and importance of brown adipose tissue in adult humans. New Eng J Med 2009; 360:1509-17; PMID:19357406; http://dx.doi.org/10.1056/NEJMoa0810780
   PubMed Web of Science ®Google Scholar
• van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. New Eng J Med 2009; 360:1500-8; PMID:19357405; http://dx.doi.org/10.1056/NEJMoa0808718
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Met 2007; 293:E444-52; PMID:17473055; http://dx.doi.org/10.1152/ajpendo.00691.2006
   PubMed Web of Science ®Google Scholar
• Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009; 58:1526-31; PMID:19401428; http://dx.doi.org/10.2337/db09-0530
   PubMed Web of Science ®Google Scholar
• Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150:366-76; PMID:22796012; http://dx.doi.org/10.1016/j.cell.2012.05.016
   PubMed Web of Science ®Google Scholar
• Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 2014; 10:24-36; PMID:24146030; http://dx.doi.org/10.1038/nrendo.2013.204
   PubMed Web of Science ®Google Scholar
• Jespersen NZ, Larsen TJ, Peijs L, Daugaard S, Homoe P, Loft A, de Jong J, Mathur N, Cannon B, Nedergaard J, et al. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Met 2013; 17:798-805; PMID:23663743; http://dx.doi.org/10.1016/j.cmet.2013.04.011
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Cannon B. How brown is brown fat? It depends where you look. Nat Med 2013; 19:540-1; PMID:23652104; http://dx.doi.org/10.1038/nm.3187
   PubMed Web of Science ®Google Scholar
• Liu W, Shan T, Yang X, Liang S, Zhang P, Liu Y, Liu X, Kuang S. A heterogeneous lineage origin underlies the phenotypic and molecular differences of white and beige adipocytes. J Cell Sci 2013; 126:3527-32; PMID:23781029; http://dx.doi.org/10.1242/jcs.124321
   PubMed Web of Science ®Google Scholar
• Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 2013; 19:1338-44; PMID:23995282; http://dx.doi.org/10.1038/nm.3324
   PubMed Web of Science ®Google Scholar
• Lee YH, Petkova AP, Mottillo EP, Granneman JG. In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding. Cell Metab 2012; 15:480-91; PMID:22482730; http://dx.doi.org/10.1016/j.cmet.2012.03.009
   PubMed Web of Science ®Google Scholar
• Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De Matteis R, Cinti S. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Met 2010; 298:E1244-53; PMID:20354155; http://dx.doi.org/10.1152/ajpendo.00600.2009
   PubMed Web of Science ®Google Scholar
• Rosenwald M, Perdikari A, Rulicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 2013; 15:659-67; PMID:23624403; http://dx.doi.org/10.1038/ncb2740
   PubMed Web of Science ®Google Scholar
• Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 2014; 156:304-16; PMID:24439384; http://dx.doi.org/10.1016/j.cell.2013.12.021
   PubMed Web of Science ®Google Scholar
• Bi P, Shan T, Liu W, Yue F, Yang X, Liang XR, Wang J, Li J, Carlesso N, Liu X, et al. Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat Med 2014; PMID:25038826
   PubMedGoogle Scholar
• Wan DC, Longaker MT. Fat or fiction: origins matter. Cell Met 2014; 19:900-1; PMID:24896537; http://dx.doi.org/10.1016/j.cmet.2014.05.007
   PubMedGoogle Scholar
• Sanchez-Gurmaches J, Guertin DA. Adipocyte lineages: tracing back the origins of fat. Biochimica et Biophysica Acta 2014; 1842:340-51; PMID:23747579; http://dx.doi.org/10.1016/j.bbadis.2013.05.027
   PubMedGoogle Scholar
• Sanchez-Gurmaches J, Guertin DA. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun 2014; 5:4099; PMID:24942009; http://dx.doi.org/10.1038/ncomms5099
   PubMed Web of Science ®Google Scholar
• Chau YY, Bandiera R, Serrels A, Martinez-Estrada OM, Qing W, Lee M, Slight J, Thornburn A, Berry R, McHaffie S, et al. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nat Cell Biol 2014; PMID:24609269
   PubMedGoogle Scholar
• Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell 2007; 131:242-56; PMID:17956727; http://dx.doi.org/10.1016/j.cell.2007.10.004
   PubMed Web of Science ®Google Scholar
• Addison O, Marcus RL, Lastayo PC, Ryan AS. Intermuscular fat: a review of the consequences and causes. Int J Endocrinol 2014; 2014:309570; PMID:24527032; http://dx.doi.org/10.1155/2014/309570
   PubMedGoogle Scholar
• Neel BA, Lin Y, Pessin JE. Skeletal muscle autophagy: a new metabolic regulator. Trends Endocrinol Met: TEM 2013; 24:635-43; PMID:24182456; http://dx.doi.org/10.1016/j.tem.2013.09.004
   PubMed Web of Science ®Google Scholar
• Brault JJ, Dohm GL, Houmard JA. Twenty-two skeletal muscle metabolism and obesity. Handbook Obesity: Epidemol, Etiol, Physiopathol 2014; 1:249; http://dx.doi.org/10.1201/b16473-25
   Google Scholar
• Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 2013; 93:993-1017; PMID:23899560; http://dx.doi.org/10.1152/physrev.00038.2012
   PubMed Web of Science ®Google Scholar
• JorgensenO’Neill HM. AMPK and exercise: glucose uptake and insulin sensitivity. Diabetes Met J 2013; 37:1-21; http://dx.doi.org/10.4093/dmj.2013.37.1.1
   Google Scholar
• Friedrichsen M, Mortensen B, Pehmoller C, Birk JB, Wojtaszewski JF. Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity. Mol Cell Endocrinol 2013; 366:204-14; PMID:22796442; http://dx.doi.org/10.1016/j.mce.2012.06.013
   PubMed Web of Science ®Google Scholar
• Barnes BR, Marklund S, Steiler TL, Walter M, Hjalm G, Amarger V, Mahlapuu M, Leng Y, Johansson C, Galuska D, et al. The 5′-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J Biol Chem 2004; 279:38441-7; PMID:15247217; http://dx.doi.org/10.1074/jbc.M405533200
   PubMed Web of Science ®Google Scholar
• Jorgensen SB, Viollet B, Andreelli F, Frosig C, Birk JB, Schjerling P, Vaulont S, Richter EA, Wojtaszewski JF. Knockout of the alpha2 but not alpha1 5’-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem 2004; 279:1070-9; PMID:14573616; http://dx.doi.org/10.1074/jbc.M306205200
   PubMed Web of Science ®Google Scholar
• Steinberg GR, O’Neill HM, Dzamko NL, Galic S, Naim T, Koopman R, Jorgensen SB, Honeyman J, Hewitt K, Chen ZP, et al. Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity. J Biol Chem 2010; 285:37198-209; PMID:20855892; http://dx.doi.org/10.1074/jbc.M110.102434
   PubMed Web of Science ®Google Scholar
• Dasgupta B, Ju JS, Sasaki Y, Liu X, Jung SR, Higashida K, Lindquist D, Milbrandt J. The AMPK beta2 subunit is required for energy homeostasis during metabolic stress. Mol Cell Biol 2012; 32:2837-48; PMID:22586267; http://dx.doi.org/10.1128/MCB.05853-11
   PubMedGoogle Scholar
• O’Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB, Schertzer JD, Shyroka O, Kiens B, van Denderen BJ, Tarnopolsky MA, et al. AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Nat Acad Sci U S A 2011; 108:16092-7; http://dx.doi.org/10.1073/pnas.1105062108
   PubMed Web of Science ®Google Scholar
• Merry TL, Steinberg GR, Lynch GS, McConell GK. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. Am J Physiol Endocrinol Met 2010; 298:E577-85; PMID:20009026; http://dx.doi.org/10.1152/ajpendo.00239.2009
   PubMed Web of Science ®Google Scholar
• Hadley RD, Whaley JW, Askins DG, Jr. Treatment of type 2 diabetes: a review of metformin in clinical practice. J South Carolina Med Assoc 1998; 94:12-5.
   PubMedGoogle Scholar
• Dunn CJ, Peters DH. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995; 49:721-49; PMID:7601013; http://dx.doi.org/10.2165/00003495-199549050-00007
   PubMed Web of Science ®Google Scholar
• Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PloS One 2013; 8:e71583; PMID:23936520; http://dx.doi.org/10.1371/journal.pone.0071583
   PubMed Web of Science ®Google Scholar
• Dolan PL, Tapscott EB, Dorton PJ, Dohm GL. Contractile activity restores insulin responsiveness in skeletal muscle of obese Zucker rats. Biochem J 1993; 289 (Pt 2):423-6; PMID:8424787
   PubMedGoogle Scholar
• Azevedo JL Jr, Carey JO, Pories WJ, Morris PG, Dohm GL. Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle. Diabetes 1995; 44:695-8; PMID:7789635; http://dx.doi.org/10.2337/diab.44.6.695
   PubMedGoogle Scholar
• Blaak EE. Basic disturbances in skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus. Proc Nutr Soc 2004; 63:323-30; PMID:15294050; http://dx.doi.org/10.1079/PNS2004361
   PubMedGoogle Scholar
• Wells GD, Noseworthy MD, Hamilton J, Tarnopolski M, Tein I. Skeletal muscle metabolic dysfunction in obesity and metabolic syndrome. Can J Neurol Sci Le J Can Des Sci Neurologiques 2008; 35:31-40; PMID:18380275
   PubMed Web of Science ®Google Scholar
• Katsanos CS, Mandarino LJ. Protein metabolism in human obesity: a shift in focus from whole-body to skeletal muscle. Obesity 2011; 19:469-75; PMID:21164506; http://dx.doi.org/10.1038/oby.2010.290
   PubMedGoogle Scholar
• Pal M, Febbraio MA, Whitham M. From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol 2014; 92:331-9; PMID:24751614; http://dx.doi.org/10.1038/icb.2014.16
   PubMed Web of Science ®Google Scholar
• Eckardt K, Gorgens SW, Raschke S, Eckel J. Myokines in insulin resistance and type 2 diabetes. Diabetologia 2014; 57:1087-99; PMID:24676645; http://dx.doi.org/10.1007/s00125-014-3224-x
   PubMed Web of Science ®Google Scholar
• Raschke S, Eckel J. Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise. Mediat Inflamm 2013; 2013:320724; PMID:23861558; http://dx.doi.org/10.1155/2013/320724
   PubMed Web of Science ®Google Scholar
• Pedersen L, Hojman P. Muscle-to-organ cross talk mediated by myokines. Adipocyte 2012; 1:164-7; PMID:23700527; http://dx.doi.org/10.4161/adip.20344
   PubMedGoogle Scholar
• Teufel A, Malik N, Mukhopadhyay M, Westphal H. Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes. Gene 2002; 297:79-83; PMID:12384288; http://dx.doi.org/10.1016/S0378-1119(02)00828-4
   PubMed Web of Science ®Google Scholar
• Ferrer-Martinez A, Ruiz-Lozano P, Chien KR. Mouse PeP: a novel peroxisomal protein linked to myoblast differentiation and development. Dev Dyn: An Off Pub Am Assoc Anatomists 2002; 224:154-67; PMID:12112469; http://dx.doi.org/10.1002/dvdy.10099
   PubMed Web of Science ®Google Scholar
• Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metab: Clin Exp 2012; 61:1725-38; PMID:23018146; http://dx.doi.org/10.1016/j.metabol.2012.09.002
   PubMed Web of Science ®Google Scholar
• Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1alphaFNDC5 pathway. Cell Metab 2013; 18:649-59; PMID:24120943; http://dx.doi.org/10.1016/j.cmet.2013.09.008
   PubMed Web of Science ®Google Scholar
• Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481:463-8; PMID:22237023; http://dx.doi.org/10.1038/nature10777
   PubMed Web of Science ®Google Scholar
• Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y, Qi L, Zhang M, Wang X, Cui T, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 2014; 63:514-25; PMID:24150604; http://dx.doi.org/10.2337/db13-1106
   PubMed Web of Science ®Google Scholar
• Pedersen BK. Exercise-induced myokines and their role in chronic diseases. Brain, Behav, Immun 2011; 25:811-6; PMID:21354469; http://dx.doi.org/10.1016/j.bbi.2011.02.010
   PubMed Web of Science ®Google Scholar
• Keipert S, Ost M, Johann K, Imber F, Jastroch M, van Schothorst EM, Keijer J, Klaus S. Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine. Am J Physiol Endocrinol Metab 2014; 306:E469-82; PMID:24347058; http://dx.doi.org/10.1152/ajpendo.00330.2013
   PubMed Web of Science ®Google Scholar
• Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 2014; 19:302-9; PMID:24506871; http://dx.doi.org/10.1016/j.cmet.2013.12.017
   PubMed Web of Science ®Google Scholar
• Vaughan RA, Gannon NP, Barberena MA, Garcia-Smith R, Bisoffi M, Mermier CM, Conn CA, Trujillo KA. Characterization of the metabolic effects of Irisin on skeletal muscle in vitro. Diabetes, Obes Metab 2014; 16:711-8; PMID:24476050; http://dx.doi.org/10.1111/dom.12268
   PubMed Web of Science ®Google Scholar
• Erickson HP. Irisin and FNDC5 in retrospect: an exercise hormone or a transmembrane receptor? Adipocyte 2013; 2:289-93; PMID:24052909; http://dx.doi.org/10.4161/adip.26082
   PubMedGoogle Scholar
• Sanchis-Gomar F, Alis R, Pareja-Galeano H, Romagnoli M, Perez-Quilis C. Inconsistency in circulating irisin levels: what is really happening? Horm Metab Res  Hormon- und Stoffwechselforschung 1501; Horm et Metab 2014.
   Google Scholar
• Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 2014; 281:739-49; PMID:24237962; http://dx.doi.org/10.1111/febs.12619
   PubMed Web of Science ®Google Scholar
• Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L, Srbecky M, Imrich R, Kyselovicova O, Belan V, et al. Are skeletal muscle & adipose tissue Fndc5 gene expression and irisin release affected by obesity, diabetes and exercise? in vivo & in vitro studies. Journal of Physiol 2014; 592:1091-107; PMID:24297848; http://dx.doi.org/10.1113/jphysiol.2013.264655
   PubMed Web of Science ®Google Scholar
• Crujeiras AB, Zulet MA, Lopez-Legarrea P, de la Iglesia R, Pardo M, Carreira MC, Martinez JA, Casanueva FF. Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients. Metab: Clin Exp 2013; 63:520-31; PMID:24439241; http://dx.doi.org/10.1016/j.metabol.2013.12.007
   PubMedGoogle Scholar
• Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T, et al. Evidence against a beneficial effect of irisin in humans. PloS One 2013; 8:e73680; PMID:24040023; http://dx.doi.org/10.1371/journal.pone.0073680
   PubMed Web of Science ®Google Scholar
• Bostrom PA, Fernandez-Real JM, Mantzoros C. Irisin in humans: recent advances and questions for future research. Metab: Clin Exp 2014; 63:178-80; PMID:24342075; http://dx.doi.org/10.1016/j.metabol.2013.11.009
   PubMed Web of Science ®Google Scholar
• McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Nat Acad Sci U S A 1997; 94:12457-61; PMID:9356471; http://dx.doi.org/10.1073/pnas.94.23.12457
   PubMed Web of Science ®Google Scholar
• Grobet L, Martin LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J, Schoeberlein A, Dunner S, Menissier F, Massabanda J, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet 1997; 17:71-4; PMID:9288100; http://dx.doi.org/10.1038/ng0997-71
   PubMed Web of Science ®Google Scholar
• Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. New Eng J med 2004; 350:2682-8; PMID:15215484; http://dx.doi.org/10.1056/NEJMoa040933
   PubMed Web of Science ®Google Scholar
• Kawada S, Tachi C, Ishii N. Content and localization of myostatin in mouse skeletal muscles during aging, mechanical unloading and reloading. J Muscle Res Cell Motil 2001; 22:627-33; PMID:12222823; http://dx.doi.org/10.1023/A:1016366409691
   PubMedGoogle Scholar
• Buehring B, Binkley N. Myostatin–the holy grail for muscle, bone, and fat? Curr Osteoporosis Rep 2013; 11:407-14; PMID:24072591; http://dx.doi.org/10.1007/s11914-013-0160-5
   PubMed Web of Science ®Google Scholar
• Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PloS One 2009; 4:e4937; PMID:19295913; http://dx.doi.org/10.1371/journal.pone.0004937
   PubMed Web of Science ®Google Scholar
• McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 2002; 109:595-601; PMID:11877467; http://dx.doi.org/10.1172/JCI0213562
   PubMed Web of Science ®Google Scholar
• Shan T, Liang X, Bi P, Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1alpha-Fndc5 pathway in muscle. FASEB J: Off Pub Fed Am Soc Exp Biol 2013; 27:1981-9; PMID:23362117; http://dx.doi.org/10.1096/fj.12-225755
   PubMed Web of Science ®Google Scholar
• Allen DL, Cleary AS, Speaker KJ, Lindsay SF, Uyenishi J, Reed JM, Madden MC, Mehan RS. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab 2008; 294:E918-27; PMID: 18334608; http://dx.doi.org/10.1152/ajpendo.00798.2007
   PubMed Web of Science ®Google Scholar
• Rebbapragada A, Benchabane H, Wrana JL, Celeste AJ, Attisano L. Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Mol Cell Biol 2003; 23:7230-42; PMID:14517293; http://dx.doi.org/10.1128/MCB.23.20.7230-7242.2003
   PubMed Web of Science ®Google Scholar
• Allen DL, Hittel DS, McPherron AC. Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sport Exercise 2011; 43:1828-35; PMID:21364474; http://dx.doi.org/10.1249/MSS.0b013e3182178bb4
   PubMed Web of Science ®Google Scholar
• Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med 2003; 228:706-9; PMID:12773702
   PubMed Web of Science ®Google Scholar
• Konopka AR, Douglass MD, Kaminsky LA, Jemiolo B, Trappe TA, Trappe S, Harber MP. Molecular adaptations to aerobic exercise training in skeletal muscle of older women. J Gerontol Series A, Biol Sci Med Sci 2010; 65:1201-7; PMID:20566734; http://dx.doi.org/10.1093/gerona/glq109
   PubMedGoogle Scholar
• Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle & Nerve 2013; 47:416-23; PMID:23169607; http://dx.doi.org/10.1002/mus.23539
   PubMed Web of Science ®Google Scholar
• Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PD. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J: Off Pub Fed Am Soc Exp Biol 2001; 15:2748-50; PMID:11687509
   PubMed Web of Science ®Google Scholar
• Spangenburg EE, Booth FW. Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(–) mouse. Cytokine 2006; 34:125-30; PMID:16781162; http://dx.doi.org/10.1016/j.cyto.2006.05.001
   PubMedGoogle Scholar
• Serrano AL, Baeza-Raja B, Perdiguero E, Jardi M, Munoz-Canoves P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab 2008; 7:33-44; PMID:18177723; http://dx.doi.org/10.1016/j.cmet.2007.11.011
   PubMed Web of Science ®Google Scholar
• Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 2006; 55:2688-97; PMID:17003332; http://dx.doi.org/10.2337/db05-1404
   PubMed Web of Science ®Google Scholar
• Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 2002; 87:2084-9; PMID:11994345; http://dx.doi.org/10.1210/jcem.87.5.8450
   PubMed Web of Science ®Google Scholar
• Tsigos C, Papanicolaou DA, Kyrou I, Defensor R, Mitsiadis CS, Chrousos GP. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J Clin Endocrinol Metab 1997; 82:4167-70; PMID:9398733; http://dx.doi.org/10.1210/jcem.82.12.4422
   PubMed Web of Science ®Google Scholar
• Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278:45777-84; PMID:12952969; http://dx.doi.org/10.1074/jbc.M301977200
   PubMed Web of Science ®Google Scholar
• Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007; 56:1010-3; PMID:17287468; http://dx.doi.org/10.2337/db06-1656
   PubMed Web of Science ®Google Scholar
• Golbidi S, Laher I. Exercise induced adipokine changes and the metabolic syndrome. J Diabetes Res 2014; 2014:726861; PMID:24563869; http://dx.doi.org/10.1155/2014/726861
   PubMed Web of Science ®Google Scholar
• Quinn LS. Interleukin-15: a muscle-derived cytokine regulating fat-to-lean body composition. J Anim Sci 2008; 86:E75-83; PMID:17709786; http://dx.doi.org/10.2527/jas.2007-0458
   PubMedGoogle Scholar
• Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physiol Pharmacol: An Off J Polish Physiol Soc 2010; 61:533-41; PMID:21081796
   PubMedGoogle Scholar
• Broholm C, Laye MJ, Brandt C, Vadalasetty R, Pilegaard H, Pedersen BK, Scheele C. LIF is a contraction-induced myokine stimulating human myocyte proliferation. J Appl Physiol 2011; 111:251-9; PMID:21527666; http://dx.doi.org/10.1152/japplphysiol.01399.2010
   PubMed Web of Science ®Google Scholar
• Laviola L, Natalicchio A, Giorgino F. The IGF-I signaling pathway. Curr Pharm Des 2007; 13:663-9; PMID: 17346182; http://dx.doi.org/10.2174/138161207780249146
   PubMed Web of Science ®Google Scholar
• Barton ER, Park S, James JK, Makarewich CA, Philippou A, Eletto D, Lei H, Brisson B, Ostrovsky O, Li Z, et al. Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production. FASEB J: Off Pub Fed Am Soc Exp Biol 2012; 26:3691-702; PMID:22649033; http://dx.doi.org/10.1096/fj.11-203026
   PubMedGoogle Scholar
• 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 2006; 147:2458-67; PMID:16439461; http://dx.doi.org/10.1210/en.2005-0969
   PubMed Web of Science ®Google Scholar
• Yadav A, Saini V, Arora S. MCP-1: chemoattractant with a role beyond immunity: a review. Clinica Chimica Acta; Int J Clin Chem 2010; 411:1570-9; PMID:20633546; http://dx.doi.org/10.1016/j.cca.2010.07.006
   PubMed Web of Science ®Google Scholar
• Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012; 287:11968-80; PMID:22351773; http://dx.doi.org/10.1074/jbc.M111.336834
   PubMed Web of Science ®Google Scholar
• Lim S, Choi SH, Koo BK, Kang SM, Yoon JW, Jang HC, Choi SM, Lee MG, Lee W, Shin H, et al. Effects of aerobic exercise training on C1q tumor necrosis factor alpha-related protein isoform 5 (myonectin): association with insulin resistance and mitochondrial DNA density in women. J Clin Endocrinol Metab 2012; 97:E88-93; PMID:22031510; http://dx.doi.org/10.1210/jc.2011-1743
   PubMedGoogle Scholar
• Lafortuna CL, Maffiuletti NA, Agosti F, Sartorio A. Gender variations of body composition, muscle strength and power output in morbid obesity. Int J Obes 2005; 29:833-41; PMID:15917862; http://dx.doi.org/10.1038/sj.ijo.0802955
   PubMed Web of Science ®Google Scholar
• Sakuma K, Yamaguchi A. Sarcopenic obesity and endocrinal adaptation with age. Int J Endocrinol 2013; 2013:204164; PMID:23690769; http://dx.doi.org/10.1155/2013/204164
   PubMed Web of Science ®Google Scholar
• Brady AO, Straight CR, Evans EM. Body Composition, Muscle Capacity and Physical Function in Older Adults: An Integrated Conceptual Model. J Aging Phys Activ 2013; PMID:23945551
   PubMedGoogle Scholar
• Yamada M, Moriguch Y, Mitani T, Aoyama T, Arai H. Age-dependent changes in skeletal muscle mass and visceral fat area in Japanese adults from 40 to 79 years-of-age. Geriatr Gerontol Int 2014; 14 Suppl 1:8-14; PMID:24450556; http://dx.doi.org/10.1111/ggi.12209
   PubMedGoogle Scholar
• Schaap LA, Koster A, Visser M. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons. Epidemiol Rev 2012; PMID:23221972
   PubMedGoogle Scholar
• Sen B, Guilluy C, Xie Z, Case N, Styner M, Thomas J, Oguz I, Rubin C, Burridge K, Rubin J. Mechanically induced focal adhesion assembly amplifies anti-adipogenic pathways in mesenchymal stem cells. Stem Cells 2011; 29:1829-36; PMID:21898699; http://dx.doi.org/10.1002/stem.732
   PubMed Web of Science ®Google Scholar
• Menuki K, Mori T, Sakai A, Sakuma M, Okimoto N, Shimizu Y, Kunugita N, Nakamura T. Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTHPTHrP receptor in bone marrow cells. Bone 2008; 43:613-20; PMID:18567552; http://dx.doi.org/10.1016/j.bone.2008.04.022
   PubMedGoogle Scholar
• Bazzarre TL, Kleiner SM, Litchford MD. Nutrient intake, body fat, and lipid profiles of competitive male and female bodybuilders. J Am Coll Nutr 1990; 9:136-42; PMID:2338462; http://dx.doi.org/10.1080/07315724.1990.10720362
   PubMed Web of Science ®Google Scholar
• Koohmaraie M, Shackelford SD, Wheeler TL, Lonergan SM, Doumit ME. A muscle hypertrophy condition in lamb (callipyge): characterization of effects on muscle growth and meat quality traits. J Anim Sci 1995; 73:3596-607; PMID:8655433
   PubMed Web of Science ®Google Scholar
• Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. Am J Physiol Endocrinol Metab 2008; 294:E882-8; PMID:18319352; http://dx.doi.org/10.1152/ajpendo.00769.2007
   PubMed Web of Science ®Google Scholar
• Tarnopolsky MA, Rennie CD, Robertshaw HA, Fedak-Tarnopolsky SN, Devries MC, Hamadeh MJ. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul, Integr Comp Physiol 2007; 292:R1271-8; PMID:17095651; http://dx.doi.org/10.1152/ajpregu.00472.2006
   PubMed Web of Science ®Google Scholar
• van Loon LJ, Koopman R, Manders R, van der Weegen W, van Kranenburg GP, Keizer HA. Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes. Am J Physiol Endocrinol Metab 2004; 287:E558-65; PMID:15165998; http://dx.doi.org/10.1152/ajpendo.00464.2003
   PubMed Web of Science ®Google Scholar
• Badin PM, Langin D, Moro C. Dynamics of skeletal muscle lipid pools. Trends Endocrinology Metab: TEM 2013; 24:607-15; PMID:23988586; http://dx.doi.org/10.1016/j.tem.2013.08.001
   PubMedGoogle Scholar
• Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 2001; 86:5755-61; PMID:11739435; http://dx.doi.org/10.1210/jcem.86.12.8075
   PubMed Web of Science ®Google Scholar
• van Loon LJ. Use of intramuscular triacylglycerol as a substrate source during exercise in humans. J Appl Physiol 2004; 97:1170-87; PMID:15358749; http://dx.doi.org/10.1152/japplphysiol.00368.2004
   PubMed Web of Science ®Google Scholar
• Romacho T, Elsen M, Rohrborn D, Eckel J. Adipose tissue and its role in organ crosstalk. Acta Physiologica 2014; PMID:24495317
   PubMedGoogle Scholar
• Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol 2013; 4:71; PMID:23781214; http://dx.doi.org/10.3389/fendo.2013.00071
   PubMedGoogle Scholar
• Sanchez J, Nozhenko Y, Palou A, Rodriguez AM. Free fatty acid effects on myokine production in combination with exercise mimetics. Mol Nutr Food Res 2013; 57:1456-67; PMID:23650203; http://dx.doi.org/10.1002/mnfr.201300126
   PubMed Web of Science ®Google Scholar
• Akhmedov D, Berdeaux R. The effects of obesity on skeletal muscle regeneration. Front Physiol 2013; 4:371; PMID:24381559; http://dx.doi.org/10.3389/fphys.2013.00371
   PubMedGoogle Scholar
• Fiaschi T, Magherini F, Gamberi T, Modesti PA, Modesti A. Adiponectin as a tissue regenerating hormone: more than a metabolic function. Cell Mol Life Sci: CMLS 2013; PMID:24322911
   PubMedGoogle Scholar