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Adipokines in Healthy Skeletal Muscle and Metabolic Disease

  • C. A. ColesEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 900)

Abstract

Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease.

Keywords

Adipokines Adipocytokines Adiponectin Leptin Interleukin-6 Skeletal muscle Adipose tissue Metabolism Exercise Insulin resistance Inflammation 

References

  1. Akhmedov D, Berdeaux R (2013) The effects of obesity on skeletal muscle regeneration. Front Physiol 4:1-12CrossRefGoogle Scholar
  2. Ara I, Perez-Gomez J, Vicente-Rodriguez G, Chavarren J, Dorado C, Calbet JA (2006) Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme. Br J Nutr 96:1053–1059PubMedCrossRefGoogle Scholar
  3. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83PubMedCrossRefGoogle Scholar
  4. Bashan N, Dorfman K, Tarnovscki T, Harman-Boehm I, Liberty IF, Bluher M, Ovadia S, Maymon-Zilberstein T, Potashnik R, Stumvoll M, Avinoach E, Rudich A (2007) Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity. Endocrinology 148:2955–2962PubMedCrossRefGoogle Scholar
  5. Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85:3338–3342PubMedGoogle Scholar
  6. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87:2084–2089PubMedCrossRefGoogle Scholar
  7. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12PubMedGoogle Scholar
  8. Beavers KM, Brinkley TE, Nicklas BJ (2010) Effect of exercise training on chronic inflammation. Clin Chim Acta 411:785–793PubMedPubMedCentralCrossRefGoogle Scholar
  9. Berggren JR, Hulver MW, Houmard JA (2005) Fat as an endocrine organ: influence of exercise. J Appl Physiol 99:757–764PubMedCrossRefGoogle Scholar
  10. Bjursell M, Ahnmark A, Bohlooly YM, William-Olsson L, Rhedin M, Peng XR, Ploj K, Gerdin AK, Arnerup G, Elmgren A, Berg AL, Oscarsson J, Linden D (2007) Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes 56:583–593PubMedCrossRefGoogle Scholar
  11. Boden G, Chen X, Mozzoli M, Ryan I (1996) Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 81:3419–3423PubMedGoogle Scholar
  12. Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z (2010) Review on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br J Sports Med 44:620–630PubMedCrossRefGoogle Scholar
  13. Bruce CR, Dyck DJ (2004) Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am J Physiol Endocrinol Metab 287:E616–E621PubMedCrossRefGoogle Scholar
  14. Bruce CR, Mertz VA, Heigenhauser GJ, Dyck DJ (2005) The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes 54:3154–3160PubMedCrossRefGoogle Scholar
  15. Bruun JM, Helge JW, Richelsen B, Stallknecht B (2006) Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am J Physiol Endocrinol Metab 290:E961–E967PubMedCrossRefGoogle Scholar
  16. Bruunsgaard H (2005) Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 78:819–835PubMedCrossRefGoogle Scholar
  17. Cao H (2014) Adipocytokines in obesity and metabolic disease. J Endocrinol 220:T47–T59PubMedPubMedCentralCrossRefGoogle Scholar
  18. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA (2006) Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55:2688–2697PubMedCrossRefGoogle Scholar
  19. Ceddia RB, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G (2005) Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia 48:132–139PubMedCrossRefGoogle Scholar
  20. Cha SH, Rodgers JT, Puigserver P, Chohnan S, Lane MD (2006) Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: role of PGC-1alpha. Proc Natl Acad Sci U S A 103:15410–15415PubMedPubMedCentralCrossRefGoogle Scholar
  21. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295PubMedCrossRefGoogle Scholar
  22. Consitt LA, Bell JA, Houmard JA (2009) Intramuscular lipid metabolism, insulin action, and obesity. IUBMB Life 61:47–55PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cooney GJ, Thompson AL, Furler SM, Ye J, Kraegen EW (2002) Muscle long-chain acyl CoA esters and insulin resistance. Ann N Y Acad Sci 967:196–207PubMedCrossRefGoogle Scholar
  24. Cotillard A, Poitou C, Torcivia A, Bouillot JL, Dietrich A, Kloting N, Gregoire C, Lolmede K, Bluher M, Clement K (2014) Adipocyte size threshold matters: link with risk of type 2 diabetes and improved insulin resistance after gastric bypass. J Clin Endocrinol Metab 99:E1466–E1470PubMedCrossRefGoogle Scholar
  25. Csehi SB, Mathieu S, Seifert U, Lange A, Zweyer M, Wernig A, Adam D (2005) Tumor necrosis factor (TNF) interferes with insulin signaling through the p55 TNF receptor death domain. Biochem Biophys Res Commun 329:397–405PubMedCrossRefGoogle Scholar
  26. Desgorces FD, Chennaoui M, Gomez-Merino D, Drogou C, Bonneau D, Guezennec CY (2004) Leptin, catecholamines and free fatty acids related to reduced recovery delays after training. Eur J Appl Physiol 93:153–158PubMedCrossRefGoogle Scholar
  27. Di Gregorio GB, Hensley L, Lu T, Ranganathan G, Kern PA (2004) Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab 287:E182–E187PubMedCrossRefGoogle Scholar
  28. Dunn SL, Bjornholm M, Bates SH, Chen Z, Seifert M, Myers MG Jr (2005) Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. Mol Endocrinol 19:925–938PubMedCrossRefGoogle Scholar
  29. Duntas LH, Popovic V, Panotopoulos G (2004) Adiponectin: novelties in metabolism and hormonal regulation. Nutr Neurosci 7:195–200PubMedCrossRefGoogle Scholar
  30. Eriksson M, Johnson O, Boman K, Hallmans G, Hellsten G, Nilsson TK, Soderberg S (2008) Improved fibrinolytic activity during exercise may be an effect of the adipocyte-derived hormones leptin and adiponectin. Thromb Res 122:701–708PubMedCrossRefGoogle Scholar
  31. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145:2273–2282PubMedCrossRefGoogle Scholar
  32. Fatouros IG, Tournis S, Leontsini D, Jamurtas AZ, Sxina M, Thomakos P, Manousaki M, Douroudos I, Taxildaris K, Mitrakou A (2005) Leptin and adiponectin responses in overweight inactive elderly following resistance training and detraining are intensity related. J Clin Endocrinol Metab 90:5970–5977PubMedCrossRefGoogle Scholar
  33. Febbraio MA, Steensberg A, Keller C, Starkie RL, Nielsen HB, Krustrup P, Ott P, Secher NH, Pedersen BK (2003) Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J Physiol 549:607–612PubMedPubMedCentralCrossRefGoogle Scholar
  34. Ferguson MA, White LJ, McCoy S, Kim HW, Petty T, Wilsey J (2004) Plasma adiponectin response to acute exercise in healthy subjects. Eur J Appl Physiol 91:324–329PubMedCrossRefGoogle Scholar
  35. Fernandez-Real JM, Broch M, Vendrell J, Gutierrez C, Casamitjana R, Pugeat M, Richart C, Ricart W (2000) Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes 49:517–520PubMedCrossRefGoogle Scholar
  36. Fischer CP, Plomgaard P, Hansen AK, Pilegaard H, Saltin B, Pedersen BK (2004) Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am J Physiol Endocrinol Metab 287:E1189–E1194PubMedCrossRefGoogle Scholar
  37. Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedPubMedCentralCrossRefGoogle Scholar
  38. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS (1995) Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1:1311–1314PubMedCrossRefGoogle Scholar
  39. Friedrichsen M, Mortensen B, Pehmoller C, Birk JB, Wojtaszewski JF (2013) Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity. Mol Cell Endocrinol 366:204–214PubMedCrossRefGoogle Scholar
  40. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98:2005–2010PubMedPubMedCentralCrossRefGoogle Scholar
  41. Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ, Ye J (2002) Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 277:48115–48121PubMedCrossRefGoogle Scholar
  42. Gao S, Kinzig KP, Aja S, Scott KA, Keung W, Kelly S, Strynadka K, Chohnan S, Smith WW, Tamashiro KL, Ladenheim EE, Ronnett GV, Tu Y, Birnbaum MJ, Lopaschuk GD, Moran TH (2007) Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci U S A 104:17358–17363PubMedPubMedCentralCrossRefGoogle Scholar
  43. Golbidi S, Laher I (2014) Exercise induced adipokine changes and the metabolic syndrome. J Diabetes Res 2014:726861PubMedPubMedCentralCrossRefGoogle Scholar
  44. Goodpaster BH, Theriault R, Watkins SC, Kelley DE (2000) Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism 49:467–472PubMedCrossRefGoogle Scholar
  45. Gulli RA, Tishinsky JM, MacDonald T, Robinson LE, Wright DC, Dyck DJ (2012) Exercise restores insulin, but not adiponectin, response in skeletal muscle of high-fat fed rodents. Am J Physiol Regul Integr Comp Physiol 303:R1062–R1070PubMedCrossRefGoogle Scholar
  46. Halaas J, Gajiwala K, Maffei M, Cohen S, Chait B, Rabinowitz D, Lallone R, Burley S, Friedman J (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546PubMedCrossRefGoogle Scholar
  47. Hamilton BS, Paglia D, Kwan AY, Deitel M (1995) Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1:953–956PubMedCrossRefGoogle Scholar
  48. Hilton TN, Tuttle LJ, Bohnert KL, Mueller MJ, Sinacore DR (2008) Excessive adipose tissue infiltration in skeletal muscle in individuals with obesity, diabetes mellitus, and peripheral neuropathy: association with performance and function. Phys Ther 88:1336–1344PubMedPubMedCentralCrossRefGoogle Scholar
  49. Hiscock N, Chan MH, Bisucci T, Darby IA, Febbraio MA (2004) Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J 18:992–994PubMedGoogle Scholar
  50. Hla T, Kolesnick R (2014) C16:0-ceramide signals insulin resistance. Cell Metab 20:703–705PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hoene M, Weigert C (2008) The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes Rev 9:20–29PubMedGoogle Scholar
  52. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE (2011) Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 17:55–63PubMedPubMedCentralCrossRefGoogle Scholar
  53. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91PubMedCrossRefGoogle Scholar
  54. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM (1994) Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A 91:4854–4858PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:665–668PubMedCrossRefGoogle Scholar
  56. Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133PubMedCrossRefGoogle Scholar
  57. Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C, Flier JS (2004) Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 10:734–738PubMedCrossRefGoogle Scholar
  58. Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703PubMedCrossRefGoogle Scholar
  59. Hu Z, Wang H, Lee IH, Modi S, Wang X, Du J, Mitch WE (2010) PTEN inhibition improves muscle regeneration in mice fed a high-fat diet. Diabetes 59:1312–1320PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz CA, Sinha MK, Pories WJ, MacDonald KG, Dohm GL (2002) Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 283:E861–E865PubMedCrossRefGoogle Scholar
  61. Ikeda S, Tamura Y, Kakehi S, Takeno K, Kawaguchi M, Watanabe T, Sato F, Ogihara T, Kanazawa A, Fujitani Y, Kawamori R, Watada H (2013) Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle. Biochem Biophys Res Commun 441:36–41PubMedCrossRefGoogle Scholar
  62. Inukai K, Nakashima Y, Watanabe M, Takata N, Sawa T, Kurihara S, Awata T, Katayama S (2005) Regulation of adiponectin receptor gene expression in diabetic mice. Am J Physiol Endocrinol Metab 288:E876–E882PubMedCrossRefGoogle Scholar
  63. Johnston AM, Pirola L, Van Obberghen E (2003) Molecular mechanisms of insulin receptor substrate protein-mediated modulation of insulin signalling. FEBS Lett 546:32–36PubMedCrossRefGoogle Scholar
  64. Jorgensen SB, O’Neill HM, Sylow L, Honeyman J, Hewitt KA, Palanivel R, Fullerton MD, Oberg L, Balendran A, Galic S, van der Poel C, Trounce IA, Lynch GS, Schertzer JD, Steinberg GR (2013) Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes 62:56–64PubMedPubMedCentralCrossRefGoogle Scholar
  65. Jurimae J, Maestu J, Jurimae T (2003) Leptin as a marker of training stress in highly trained male rowers? Eur J Appl Physiol 90:533–538PubMedCrossRefGoogle Scholar
  66. Jurimae J, Purge P, Jurimae T (2005) Adiponectin is altered after maximal exercise in highly trained male rowers. Eur J Appl Physiol 93:502–505PubMedCrossRefGoogle Scholar
  67. Jurimae J, Purge P, Jurimae T (2007) Effect of prolonged training period on plasma adiponectin in elite male rowers. Horm Metab Res 39:519–523PubMedCrossRefGoogle Scholar
  68. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25PubMedCrossRefGoogle Scholar
  69. Kandasamy AD, Sung MM, Boisvenue JJ, Barr AJ, Dyck JR (2012) Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice. Nutr Diabetes 2:e45PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kawanishi N, Yano H, Yokogawa Y, Suzuki K (2010) Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc Immunol Rev 16:105–118PubMedGoogle Scholar
  71. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PD (2001) Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J 15:2748–50Google Scholar
  72. Keller C, Steensberg A, Hansen AK, Fischer CP, Plomgaard P, Pedersen BK (2005) Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol 99:2075–2079PubMedCrossRefGoogle Scholar
  73. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751PubMedGoogle Scholar
  74. Keung W, Palaniyappan A, Lopaschuk GD (2011) Chronic central leptin decreases food intake and improves glucose tolerance in diet-induced obese mice independent of hypothalamic malonyl CoA levels and skeletal muscle insulin sensitivity. Endocrinology 152:4127–4137PubMedCrossRefGoogle Scholar
  75. Keuper M, Bluher M, Schon MR, Moller P, Dzyakanchuk A, Amrein K, Debatin KM, Wabitsch M, Fischer-Posovszky P (2011) An inflammatory micro-environment promotes human adipocyte apoptosis. Mol Cell Endocrinol 339:105–113PubMedCrossRefGoogle Scholar
  76. Kiens B (2006) Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 86:205–243PubMedCrossRefGoogle Scholar
  77. Kloting N, Bluher M (2014) Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 15:277–287PubMedCrossRefGoogle Scholar
  78. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA (2003) Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52:2784–2789PubMedCrossRefGoogle Scholar
  79. Klover PJ, Clementi AH, Mooney RA (2005) Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology 146:3417–3427PubMedCrossRefGoogle Scholar
  80. Koerner A, Kratzsch J, Kiess W (2005) Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come. Best Pract Res Clin Endocrinol Metab 19:525–546PubMedCrossRefGoogle Scholar
  81. Kovsan J, Bluher M, Tarnovscki T, Kloting N, Kirshtein B, Madar L, Shai I, Golan R, Harman-Boehm I, Schon MR, Greenberg AS, Elazar Z, Bashan N, Rudich A (2011) Altered autophagy in human adipose tissues in obesity. J Clin Endocrinol Metab 96:E268–E277PubMedCrossRefGoogle Scholar
  82. Kraegen EW, Cooney GJ (2008) Free fatty acids and skeletal muscle insulin resistance. Curr Opin Lipidol 19:235–241PubMedCrossRefGoogle Scholar
  83. Kraemer RR, Castracane VD (2007) Exercise and humoral mediators of peripheral energy balance: ghrelin and adiponectin. Exp Biol Med (Maywood) 232:184–194Google Scholar
  84. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda T (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277:25863–25866PubMedCrossRefGoogle Scholar
  85. Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H, Kozono H, Takamoto I, Okamoto S, Shiuchi T, Suzuki R, Satoh H, Tsuchida A, Moroi M, Sugi K, Noda T, Ebinuma H, Ueta Y, Kondo T, Araki E, Ezaki O, Nagai R, Tobe K, Terauchi Y, Ueki K, Minokoshi Y, Kadowaki T (2007) Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab 6:55–68PubMedCrossRefGoogle Scholar
  86. Legakis IN, Mantzouridis T, Saramantis A, Lakka-Papadodima E (2004) Rapid decrease of leptin in middle-aged sedentary individuals after 20 minutes of vigorous exercise with early recovery after the termination of the test. J Endocrinol Investig 27:117–120CrossRefGoogle Scholar
  87. Li L, Pan R, Li R, Niemann B, Aurich AC, Chen Y, Rohrbach S (2011) Mitochondrial biogenesis and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes 60:157–167PubMedPubMedCentralCrossRefGoogle Scholar
  88. Lim S, Choi SH, Jeong IK, Kim JH, Moon MK, Park KS, Lee HK, Kim YB, Jang HC (2008) Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J Clin Endocrinol Metab 93:2263–2268PubMedCrossRefGoogle Scholar
  89. Liu Y, Michael MD, Kash S, Bensch WR, Monia BP, Murray SF, Otto KA, Syed SK, Bhanot S, Sloop KW, Sullivan JM, Reifel-Miller A (2007) Deficiency of adiponectin receptor 2 reduces diet-induced insulin resistance but promotes type 2 diabetes. Endocrinology 148:683–692PubMedCrossRefGoogle Scholar
  90. Lonnqvist F, Arner P, Nordfors L, Schalling M (1995) Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1:950–953PubMedCrossRefGoogle Scholar
  91. Lukic L, Lalic NM, Rajkovic N, Jotic A, Lalic K, Milicic T, Seferovic JP, Macesic M, Gajovic JS (2014) Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention. Int J Environ Res Public Health 11:3586–3598PubMedPubMedCentralCrossRefGoogle Scholar
  92. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184PubMedPubMedCentralCrossRefGoogle Scholar
  93. Lyngsø D, Simonsen L, Bülow J (2002) Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise. J Physiol 543:373–378PubMedPubMedCentralCrossRefGoogle Scholar
  94. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8:731–737PubMedCrossRefGoogle Scholar
  95. Maffei M, Stoffel M, Barone M, Moon B, Dammerman M, Ravussin E, Bogardus C, Ludwig DS, Flier JS, Talley M et al (1996) Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes 45:679–682PubMedCrossRefGoogle Scholar
  96. Malenfant P, Joanisse DR, Theriault R, Goodpaster BH, Kelley DE, Simoneau JA (2001) Fat content in individual muscle fibers of lean and obese subjects. Int J Obes Relat Metab Disord 25:1316–1321PubMedCrossRefGoogle Scholar
  97. Masaki T, Chiba S, Yasuda T, Tsubone T, Kakuma T, Shimomura I, Funahashi T, Matsuzawa Y, Yoshimatsu H (2003) Peripheral, but not central, administration of adiponectin reduces visceral adiposity and upregulates the expression of uncoupling protein in agouti yellow (Ay/a) obese mice. Diabetes 52:2266–2273PubMedCrossRefGoogle Scholar
  98. Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, Becker C, Franchi L, Yoshihara E, Chen Z, Mullooly N, Mielke LA, Harris J, Coll RC, Mills KH, Mok KH, Newsholme P, Nunez G, Yodoi J, Kahn SE, Lavelle EC, O’Neill LA (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol 11:897–904PubMedPubMedCentralCrossRefGoogle Scholar
  99. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33PubMedCrossRefGoogle Scholar
  100. Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Bronneke HS, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Bruning JC (2014) Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 15:423–430PubMedPubMedCentralCrossRefGoogle Scholar
  101. McFarlin BK, Flynn MG, Campbell WW, Stewart LK, Timmerman KL (2004) TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Med Sci Sports Exerc 36:1876–1883PubMedCrossRefGoogle Scholar
  102. Meier U, Gressner AM (2004) Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 50:1511–1525PubMedCrossRefGoogle Scholar
  103. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343PubMedCrossRefGoogle Scholar
  104. Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S (2008) Role of hypothalamic AMP-kinase in food intake regulation. Nutrition 24:786–790PubMedCrossRefGoogle Scholar
  105. Minokoshi Y, Toda C, Okamoto S (2012) Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle. Indian J Endocrinol Metab 16:S562–S568PubMedPubMedCentralCrossRefGoogle Scholar
  106. Mitrou P, Lambadiari V, Maratou E, Boutati E, Komesidou V, Papakonstantinou A, Raptis SA, Dimitriadis G (2011) Skeletal muscle insulin resistance in morbid obesity: the role of interleukin-6 and leptin. Exp Clin Endocrinol Diabetes 119:484–489PubMedCrossRefGoogle Scholar
  107. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 82:4196–4200PubMedGoogle Scholar
  108. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908PubMedCrossRefGoogle Scholar
  109. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A (2004) Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10:739–743PubMedCrossRefGoogle Scholar
  110. Mullen KL, Smith AC, Junkin KA, Dyck DJ (2007) Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat-fed rats. Am J Physiol Endocrinol Metab 293:E83–E90PubMedCrossRefGoogle Scholar
  111. Muoio DM, Dohm GL, Fiedorek FT Jr, Tapscott EB, Coleman RA (1997) Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 46:1360–1363PubMedCrossRefGoogle Scholar
  112. Murakami T, Yamashita T, Iida M, Kuwajima M, Shima K (1997) A short form of leptin receptor performs signal transduction. Biochem Biophys Res Commun 231:26–29PubMedCrossRefGoogle Scholar
  113. Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L, Scherer PE (2006) Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 281:2654–2660PubMedCrossRefGoogle Scholar
  114. Obici S, Feng Z, Arduini A, Conti R, Rossetti L (2003) Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9:756–761PubMedCrossRefGoogle Scholar
  115. Olive JL, Miller GD (2001) Differential effects of maximal- and moderate-intensity runs on plasma leptin in healthy trained subjects. Nutrition 17:365–369PubMedCrossRefGoogle Scholar
  116. Ostrowski K, Rohde T, Zacho M, Asp S, Pedersen BK (1998) Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J Physiol 508:949–953PubMedPubMedCentralCrossRefGoogle Scholar
  117. Ozcelik O, Celik H, Ayar A, Serhatlioglu S, Kelestimur H (2004) Investigation of the influence of training status on the relationship between the acute exercise and serum leptin levels in obese females. Neuro Endocrinol Lett 25:381–385PubMedGoogle Scholar
  118. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB (2003) 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 163:427–436PubMedPubMedCentralCrossRefGoogle Scholar
  119. Pedersen BK (2012) Muscular interleukin-6 and its role as an energy sensor. Med Sci Sports Exerc 44:392–396PubMedCrossRefGoogle Scholar
  120. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540–543PubMedCrossRefGoogle Scholar
  121. Peraldi P, Hotamisligil GS, Buurman WA, White MF, Spiegelman BM (1996) Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem 271:13018–13022PubMedCrossRefGoogle Scholar
  122. Petersen AMW, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol 98:1154–1162PubMedCrossRefGoogle Scholar
  123. Polak J, Klimcakova E, Moro C, Viguerie N, Berlan M, Hejnova J, Richterova B, Kraus I, Langin D, Stich V (2006) Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor α in obese women. Metabolism 55:1375–1381PubMedCrossRefGoogle Scholar
  124. Punyadeera C, Zorenc AH, Koopman R, McAinch AJ, Smit E, Manders R, Keizer HA, Cameron-Smith D, van Loon LJ (2005) The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle. Eur J Endocrinol 152:427–436PubMedCrossRefGoogle Scholar
  125. Rabe K, Lehrke M, Parhofer KG, Broedl UC (2008) Adipokines and insulin resistance. Mol Med 14:741–751PubMedPubMedCentralCrossRefGoogle Scholar
  126. Rall LC, Roubenoff R, Cannon JG, Abad LW, Dinarello CA, Meydani SN (1996) Effects of progressive resistance training on immune response in aging and chronic inflammation. Med Sci Sports Exerc 28:1356–1365PubMedCrossRefGoogle Scholar
  127. Ritchie IR, Gulli RA, Stefanyk LE, Harasim E, Chabowski A, Dyck DJ (2011) Restoration of skeletal muscle leptin response does not precede the exercise-induced recovery of insulin-stimulated glucose uptake in high-fat-fed rats. Am J Physiol Regul Integr Comp Physiol 300:R492–R500PubMedCrossRefGoogle Scholar
  128. Ritchie IR, Wright DC, Dyck DJ (2014) Adiponectin is not required for exercise training-induced improvements in glucose and insulin tolerance in mice. Physiol Rep 2:1–12CrossRefGoogle Scholar
  129. Rosendal L, Søgaard K, Kjær M, Sjøgaard G, Langberg H, Kristiansen J (2005) Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise. J Appl Physiol 98:477–481PubMedCrossRefGoogle Scholar
  130. Ruderman NB, Keller C, Richard A-M, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M (2006) Interleukin-6 regulation of AMP-activated protein kinase: potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55:S48–S54PubMedCrossRefGoogle Scholar
  131. Rudich A, Kanety H, Bashan N (2007) Adipose stress-sensing kinases: linking obesity to malfunction. Trends Endocrinol Metab 18:291–299PubMedCrossRefGoogle Scholar
  132. Sabio G, Das M, Mora A, Zhang Z, Jun JY, Ko HJ, Barrett T, Kim JK, Davis RJ (2008) A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science 322:1539–1543PubMedPubMedCentralCrossRefGoogle Scholar
  133. Sadagurski M, Norquay L, Farhang J, D’Aquino K, Copps K, White MF (2010) Human IL6 enhances leptin action in mice. Diabetologia 53:525–535PubMedPubMedCentralCrossRefGoogle Scholar
  134. Sahu M, Litvin DG, Sahu A (2011) Phosphodiesterase-3B is expressed in proopiomelanocortin and neuropeptide Y neurons in the mouse hypothalamus. Neurosci Lett 505:93–97PubMedPubMedCentralCrossRefGoogle Scholar
  135. Sainz N, Rodriguez A, Catalan V, Becerril S, Ramirez B, Gomez-Ambrosi J, Fruhbeck G (2009) Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One 4:e6808PubMedPubMedCentralCrossRefGoogle Scholar
  136. Sainz N, Rodriguez A, Catalan V, Becerril S, Ramirez B, Gomez-Ambrosi J, Fruhbeck G (2010) Leptin administration downregulates the increased expression levels of genes related to oxidative stress and inflammation in the skeletal muscle of ob/ob mice. Mediat Inflamm 2010:784343Google Scholar
  137. Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwerx J (1995) Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527–529PubMedCrossRefGoogle Scholar
  138. Salans LB, Knittle JL, Hirsch J (1968) The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J Clin Invest 47:153–165PubMedPubMedCentralCrossRefGoogle Scholar
  139. Schindler R, Mancilla J, Endres S, Ghorbani R, Clark SC, Dinarello CA (1990) Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood 75:40–47PubMedGoogle Scholar
  140. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF (1996) Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97:1344–1347PubMedPubMedCentralCrossRefGoogle Scholar
  141. Sopasakis VR, Sandqvist M, Gustafson B, Hammarstedt A, Schmelz M, Yang X, Jansson PA, Smith U (2004) High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes Res 12:454–460PubMedCrossRefGoogle Scholar
  142. Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817PubMedCrossRefGoogle Scholar
  143. Starkie RL, Angus DJ, Rolland J, Hargreaves M, Febbraio MA (2000) Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. J Physiol 528:647–655PubMedPubMedCentralCrossRefGoogle Scholar
  144. Starkie RL, Rolland J, Angus DJ, Anderson MJ, Febbraio MA (2001) Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-α levels after prolonged running. Am J Physiol Cell Physiol 280:C769–C774PubMedGoogle Scholar
  145. Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 17:884–886PubMedGoogle Scholar
  146. Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Pedersen BK (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529:237–242PubMedPubMedCentralCrossRefGoogle Scholar
  147. Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK (2002) IL-6 and TNF-α expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 283:E1272–E1278PubMedCrossRefGoogle Scholar
  148. Steensberg A, Fischer CP, Sacchetti M, Keller C, Osada T, Schjerling P, van Hall G, Febbraio MA, Pedersen BK (2003) Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol 548:631–638PubMedPubMedCentralCrossRefGoogle Scholar
  149. Steinberg GR, Dyck DJ (2000) Development of leptin resistance in rat soleus muscle in response to high-fat diets. Am J Physiol Endocrinol Metab 279:E1374–E1382PubMedGoogle Scholar
  150. Steinberg GR, Bonen A, Dyck DJ (2002a) Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats. Am J Physiol Endocrinol Metab 282:E593–E600PubMedCrossRefGoogle Scholar
  151. Steinberg GR, Dyck DJ, Calles-Escandon J, Tandon NN, Luiken JJ, Glatz JF, Bonen A (2002b) Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle. J Biol Chem 277:8854–8860PubMedCrossRefGoogle Scholar
  152. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ (2002c) Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 283:E187–E192PubMedCrossRefGoogle Scholar
  153. Steinberg GR, Rush JW, Dyck DJ (2003) AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment. Am J Physiol Endocrinol Metab 284:E648–E654PubMedCrossRefGoogle Scholar
  154. Steinberg GR, Smith AC, Wormald S, Malenfant P, Collier C, Dyck DJ (2004) Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle. Am J Physiol Endocrinol Metab 286:E57–E63PubMedCrossRefGoogle Scholar
  155. Stephens JW, Hurel SJ, Lowe GD, Rumley A, Humphries SE (2007) Association between plasma IL-6, the IL6–174G > C gene variant and the metabolic syndrome in type 2 diabetes mellitus. Mol Genet Metab 90:422–428PubMedCrossRefGoogle Scholar
  156. Stuart CA, Howell ME, Cartwright BM, McCurry MP, Lee ML, Ramsey MW, Stone MH (2014) Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation. Physiolog Rep 2:1–8Google Scholar
  157. Stump CS, Henriksen EJ, Wei Y, Sowers JR (2006) The metabolic syndrome: role of skeletal muscle metabolism. Ann Med 38:389–402PubMedCrossRefGoogle Scholar
  158. Suzuki A, Okamoto S, Lee S, Saito K, Shiuchi T, Minokoshi Y (2007) Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Mol Cell Biol 27:4317–4327PubMedPubMedCentralCrossRefGoogle Scholar
  159. Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H, Niwa M, Kinoshita J, Ooka A, Kumashiro N, Igarashi Y, Kyogoku S, Maehara T, Kawasumi M, Hirose T, Kawamori R (2005) Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 90:3191–3196PubMedCrossRefGoogle Scholar
  160. Toft AD, Jensen LB, Bruunsgaard H, Ibfelt T, Halkjaer-Kristensen J, Febbraio M, Pedersen BK (2002) Cytokine response to eccentric exercise in young and elderly humans. Am J Physiol Cell Physiol 283:C289–C295PubMedCrossRefGoogle Scholar
  161. Tomas E, Tsao TS, Saha AK, Murrey HE, Zhang Cc C, Itani SI, Lodish HF, Ruderman NB (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A 99:16309–16313PubMedPubMedCentralCrossRefGoogle Scholar
  162. Troseid M, Lappegard KT, Mollnes TE, Arnesen H, Seljeflot I (2009) The effect of exercise on serum levels of interleukin-18 and components of the metabolic syndrome. Metab Syndr Relat Disord 7:579–584PubMedCrossRefGoogle Scholar
  163. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614PubMedCrossRefGoogle Scholar
  164. van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P, Hiscock N, Moller K, Saltin B, Febbraio MA, Pedersen BK (2003) Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 88:3005–3010PubMedCrossRefGoogle Scholar
  165. Van Heek M, Compton DS, France CF, Tedesco RP, Fawzi AB, Graziano MP, Sybertz EJ, Strader CD, Davis HR Jr (1997) Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest 99:385–390PubMedPubMedCentralCrossRefGoogle Scholar
  166. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188PubMedPubMedCentralCrossRefGoogle Scholar
  167. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79PubMedCrossRefGoogle Scholar
  168. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedPubMedCentralCrossRefGoogle Scholar
  169. Woo M, Isganaitis E, Cerletti M, Fitzpatrick C, Wagers AJ, Jimenez-Chillaron J, Patti ME (2011) Early life nutrition modulates muscle stem cell number: implications for muscle mass and repair. Stem Cells Dev 20:1763–1769PubMedPubMedCentralCrossRefGoogle Scholar
  170. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedPubMedCentralCrossRefGoogle Scholar
  171. Xu L, Spinas GA, Niessen M (2010) ER stress in adipocytes inhibits insulin signaling, represses lipolysis, and alters the secretion of adipokines without inhibiting glucose transport. Horm Metab Res 42:643–651PubMedCrossRefGoogle Scholar
  172. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946PubMedCrossRefGoogle Scholar
  173. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295PubMedCrossRefGoogle Scholar
  174. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13:332–339PubMedCrossRefGoogle Scholar
  175. Yaspelkis BB 3rd, Ansari L, Ramey EL, Holland GJ, Loy SF (1999) Chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Metabolism 48:671–676PubMedCrossRefGoogle Scholar
  176. Yoon MJ, Lee GY, Chung J-J, Ahn YH, Hong SH, Kim JB (2006) Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator–activated receptor α. Diabetes 55:2562–2570PubMedCrossRefGoogle Scholar
  177. Zafeiridis A, Smilios I, Considine RV, Tokmakidis SP (2003) Serum leptin responses after acute resistance exercise protocols. J Appl Physiol (1985) 94:591–597CrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Murdoch Children’s Research InstituteRoyal Children’s HospitalParkville, MelbourneAustralia

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