Advertisement

Cellular and Molecular Life Sciences

, Volume 77, Issue 1, pp 129–147 | Cite as

S100 proteins in obesity: liaisons dangereuses

  • Francesca Riuzzi
  • Sara Chiappalupi
  • Cataldo Arcuri
  • Ileana Giambanco
  • Guglielmo Sorci
  • Rosario DonatoEmail author
Review

Abstract

Obesity is an endemic pathophysiological condition and a comorbidity associated with hypercholesterolemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, and cancer. The adipose tissue of obese subjects shows hypertrophic adipocytes, adipocyte hyperplasia, and chronic low-grade inflammation. S100 proteins are Ca2+-binding proteins exclusively expressed in vertebrates in a cell-specific manner. They have been implicated in the regulation of a variety of functions acting as intracellular Ca2+ sensors transducing the Ca2+ signal and extracellular factors affecting cellular activity via ligation of a battery of membrane receptors. Certain S100 proteins, namely S100A4, the S100A8/S100A9 heterodimer and S100B, have been implicated in the pathophysiology of obesity-promoting macrophage-based inflammation via toll-like receptor 4 and/or receptor for advanced glycation end-products ligation. Also, serum levels of S100A4, S100A8/S100A9, S100A12, and S100B correlate with insulin resistance/type 2 diabetes, metabolic risk score, and fat cell size. Yet, secreted S100B appears to exert neurotrophic effects on sympathetic fibers in brown adipose tissue contributing to the larger sympathetic innervation of this latter relative to white adipose tissue. In the present review we first briefly introduce S100 proteins and then critically examine their role(s) in adipose tissue and obesity.

Keywords

Adipocyte Macrophage Cytokine Inflammation Transdifferentiation Receptor White adipose tissue Brown adipose tissue 

Abbreviations

ACTH

Adrenocorticotropin

ATM

Adipose tissue macrophage

BAT

Brown adipose tissue

BMI

Body mass index

BMP-7

Bone morphogenetic protein 7

CLSTN3β

Calsyntenin 3β

DAMP

Damage-associated molecular pattern

EEC

Enteric endocrine cell

GIP

Glucose-dependent insulinotropic polypeptide

GIPR

GIP receptor

GLP-1

Glucagon-like peptide-1

HFD

High-fat diet

IL

Interleukin

IFN-γ

Interferon-γ

LC n-3 PUFA

Long-chain omega-3 polyunsaturated fatty acids

LPS

Lipopolysaccharide

RAGE

Receptor for advanced glycation endproducts

RyR

Ryanodine receptor

SVFC

Stromal vascular fraction cell

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor-α

VAT

Visceral adipose tissue

UCP1

Uncoupling protein 1

WAT

White adipose tissue

Notes

Acknowledgements

The authors were supported by Association Française contre les Myopathies (Projects 12992 and 16812), Associazione Italiana per la Ricerca sul Cancro (Project 17581), Ministero dell’Istruzione, dell’Università e della Ricerca, Italy (PRIN 2009WBFZYM_002, PRIN 2010R8JK2X_004 and PRIN 2012N8YJC3) and Fondazione Cassa di Risparmio di Perugia (Projects 2012.0241.021, 2015.0325.021 and 2016-0136.021). The authors wish to thank the reviewers for criticism and suggestions.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    James WPT, McPherson K (2017) The costs of overweight. Lancet Public Health 2:e203–e204PubMedGoogle Scholar
  2. 2.
    Malik VS, Willett WC, Hu FB (2013) Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol 9:13–27PubMedGoogle Scholar
  3. 3.
    Kassotis CD, Stapleton HM (2019) Endocrine-mediated mechanisms of metabolic disruption and new approaches to examine the public health threat. Front Endocrinol (Lausanne) 10:39Google Scholar
  4. 4.
    NCD Risk Factor Collaboration (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population- based measurement studies with 19.2 million participants. Lancet 387:1377–1396Google Scholar
  5. 5.
    Ng M, Fleming T, Robinson M et al (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384:766–781PubMedPubMedCentralGoogle Scholar
  6. 6.
    Quail DF, Dannenberg AJ (2019) The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 15:139–154PubMedPubMedCentralGoogle Scholar
  7. 7.
    Chouchani ET, Kajimura S (2019) Metabolic adaptation and maladaptation in adipose tissue. Nat Metab 1:189–200PubMedPubMedCentralGoogle Scholar
  8. 8.
    Ghaben AL, Schere PE (2019) Adipogenesis and metabolic health. Nat Rev Mol Cell Biol 20:242–258PubMedGoogle Scholar
  9. 9.
    Haider N, Larose L (2019) Harnessing adipogenesis to prevent obesity. Adipocyte 8:1–7Google Scholar
  10. 10.
    Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMedGoogle Scholar
  11. 11.
    Haka AS, Barbosa-Lorenzi VC, Lee HJ, Falcone DJ, Hudis CA, Dannenberg AJ, Maxfield FR (2016) Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation. J Lipid Res 57:980–992PubMedPubMedCentralGoogle Scholar
  12. 12.
    Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184PubMedPubMedCentralGoogle Scholar
  13. 13.
    Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921–929PubMedPubMedCentralGoogle Scholar
  14. 14.
    Smorlesi A, Frontini A, Giordano A, Cinti S (2012) The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev 13(Suppl 2):83–96PubMedGoogle Scholar
  15. 15.
    Reilly SM, Saltiel AR (2017) Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol 13:633–643PubMedGoogle Scholar
  16. 16.
    Lee YS, Wollam J, Olefsky JM (2018) An integrated view of immunometabolism. Cell 172:22–40PubMedGoogle Scholar
  17. 17.
    Xue W, Fan Z, Li L, Lu J, Zhai Y, Zhao J (2019) The chemokine system and its role in obesity. J Cell Physiol 234:3336–3346PubMedGoogle Scholar
  18. 18.
    Koliaki C, Liatis S, Kokkinos A (2019) Obesity and cardiovascular disease: revisiting an old relationship. Metabolism 92:98–107PubMedGoogle Scholar
  19. 19.
    Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, Landerholm RW, Crouthamel M, Gozal D, Hwang S, Singh PK, Becker L (2014) Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 20:614–625PubMedPubMedCentralGoogle Scholar
  20. 20.
    Coats BR, Schoenfelt KQ, Barbosa-Lorenzi VC, Peris E, Cui C, Hoffman A, Zhou G, Fernandez S, Zhai L, Hall BA, Haka AS, Shah AM, Reardon CA, Brady MJ, Rhodes CJ, Maxfield FR, Becker L (2017) Metabolically activated adipose tissue macrophages perform detrimental and beneficial functions during diet-induced obesity. Cell Rep 20:3149–3161PubMedPubMedCentralGoogle Scholar
  21. 21.
    Hill DA, Lim HW, Kim YH, Ho WY, Foong YH, Nelson VL, Nguyen HCB, Chegireddy K, Kim J, Habertheuer A, Vallabhajosyula P, Kambayashi T, Won KJ, Lazar MA (2018) Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci USA 115:E5096–E5105PubMedGoogle Scholar
  22. 22.
    Cho KW, Zamarron BF, Muir LA, Singer K, Porsche CE, DelProposto JB, Geletka L, Meyer KA, O’Rourke RW, Lumeng CN (2016) Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance. J Immunol 197:3650–3661PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kolodin D, van Panhuys N, Li C, Magnuson AM, Cipolletta D, Miller CM, Wagers A, Germain RN, Benoist C, Mathis D (2015) Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab 21:543–557PubMedPubMedCentralGoogle Scholar
  24. 24.
    Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939PubMedPubMedCentralGoogle Scholar
  25. 25.
    Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, Wolf D, Patsch W, Rosenkranz AR, Eller P (2001) Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 60:2954–2962Google Scholar
  26. 26.
    Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y (2002) Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8:738–742PubMedGoogle Scholar
  27. 27.
    Gögebakan Ö, Andres J, Biedasek K, Mai K, Kühnen P, Krude H, Isken F, Rudovich N, Osterhoff MA, Kintscher U, Nauck M, Pfeiffer AF, Spranger J (2012) Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11β -hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids. Diabetes 61:292–300PubMedPubMedCentralGoogle Scholar
  28. 28.
    Al Massadi O, López M, Tschöp M, Diéguez C, Nogueiras R (2017) Current understanding of the hypothalamic ghrelin pathways inducing appetite and adiposity. Trends Neurosci 40:167–180PubMedGoogle Scholar
  29. 29.
    Gribble FM, Reimann F (2016) Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu Rev Physiol 78:277–299PubMedGoogle Scholar
  30. 30.
    Nauck MA, Meier JJ (2018) Incretin hormones: their role in health and disease. Diabetes Obes Metab Suppl 1:5–21Google Scholar
  31. 31.
    Dupre J, Ross SA, Watson D, Brown JC (1973) Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab 37:826–828PubMedGoogle Scholar
  32. 32.
    McLaughlin JT, McKie S (2016) Human brain responses to gastrointestinal nutrients and gut hormones. Curr Opin Pharmacol 31:8–12PubMedGoogle Scholar
  33. 33.
    Monteiro MP, Batterham RL (2017) The importance of the gastrointestinal tract in controlling food intake and regulating energy balance. Gastroenterology 152:1707–1717PubMedGoogle Scholar
  34. 34.
    Al-Najim W, Docherty NG, le Roux CW (2018) Food intake and eating behavior after bariatric surgery. Physiol Rev 98:1113–1141PubMedGoogle Scholar
  35. 35.
    Papathanasiou A, Nolen-Doerr E, Farr O, Geoffrey Mantzoros CS, Prize Harris (2018) Novel pathways regulating neuroendocrine function, energy homeostasis and metabolism in humans. Eur J Endocrinol 180:R59–R71Google Scholar
  36. 36.
    Christensen M, Vedtofte L, Holst JJ, Vilsbøll T, Knop FK (2011) Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes 60:3103–3109PubMedPubMedCentralGoogle Scholar
  37. 37.
    Pfeiffer AFH, Keyhani-Nejad F (2018) High glycemic index metabolic damage—a pivotal role of GIP and GLP-1. Trends Endocrinol Metab 29:289–299PubMedGoogle Scholar
  38. 38.
    Holst JJ (2019) From the incretin concept and the discovery of GLP-1 to today’s diabetes therapy. Front Endocrinol (Lausanne) 10:260Google Scholar
  39. 39.
    Nolen-Doerr E, Stockman MC, Rizo I (2019) Mechanism of glucagon-like peptide 1 improvements in type 2 diabetes mellitus and obesity. Curr Obes Rep.  https://doi.org/10.1007/s13679-019-00350-4 CrossRefPubMedGoogle Scholar
  40. 40.
    Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, Geczy CL (2013) Functions of S100 proteins. Curr Mol Med 13:24–57PubMedPubMedCentralGoogle Scholar
  41. 41.
    Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322:1111–1122PubMedGoogle Scholar
  42. 42.
    Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396:201–214PubMedPubMedCentralGoogle Scholar
  43. 43.
    Goyette J, Geczy CL (2011) Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids 41:821–842PubMedGoogle Scholar
  44. 44.
    Pruenster M, Vogl T, Roth J, Sperandio M (2016) S100A8/A9: from basic science to clinical application. Pharmacol Ther 167:120–131PubMedGoogle Scholar
  45. 45.
    Lim SY, Raftery MJ, Geczy CL (2011) Oxidative modifications of DAMPs suppress inflammation: the case for S100A8 and S100A9. Antioxid Redox Signal 15:2235–2248PubMedGoogle Scholar
  46. 46.
    Austermann J, Spiekermann C, Roth J (2018) S100 proteins in rheumatic diseases. Nat Rev Rheumatol 14:528–541PubMedGoogle Scholar
  47. 47.
    Donato R (2001) S100: a multigenic family of calcium modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33:637–638PubMedGoogle Scholar
  48. 48.
    Averill MM, Kerkhoff C, Bornfeldt KE (2012) S100A8 and S100A9 in cardiovascular biology and disease. Arterioscler Thromb Vasc Biol 32:223–229PubMedGoogle Scholar
  49. 49.
    Gross SR, Sin CG, Barraclough R, Rudland PS (2014) Joining S100 proteins and migration: for better or for worse, in sickness and in health. Cell Mol Life Sci 71:1551–1579PubMedGoogle Scholar
  50. 50.
    Donato R, Sorci G, Giambanco I (2017) S100A6 protein: functional roles. Cell Mol Life Sci 74:2749–2760PubMedGoogle Scholar
  51. 51.
    Riuzzi F, Sorci G, Arcuri C, Giambanco I, Bellezza I, Minelli A, Donato R (2018) Cellular and molecular mechanisms of sarcopenia: the S100B perspective. J Cachexia Sarcopenia Muscle 9:1255–1268PubMedPubMedCentralGoogle Scholar
  52. 52.
    Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J (2018) S100A8/A9 in inflammation. Front Immunol 9:1298PubMedPubMedCentralGoogle Scholar
  53. 53.
    Most P, Bernotat J, Ehlermann P, Pleger ST, Reppel M, Börries M, Niroomand F, Pieske B, Janssen PM, Eschenhagen T, Karczewski P, Smith GL, Koch WJ, Katus HA, Remppis A (2001) S100A1: a regulator of myocardial contractility. Proc Natl Acad Sci USA 98:13889–13894PubMedGoogle Scholar
  54. 54.
    Kiewitz R, Acklin C, Schäfer BW, Maco B, Uhrík B, Wuytack F, Erne P, Heizmann CW (2003) Ca2+-dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+-ATPase2a and phospholamban in the human heart. Biochem Biophys Res Commun 306:550–557PubMedGoogle Scholar
  55. 55.
    Kettlewell S, Most P, Currie S, Koch WJ, Smith GL (2005) S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes. J Mol Cell Cardiol 39:900–910PubMedGoogle Scholar
  56. 56.
    Most P, Pleger ST, Völkers M, Heidt B, Boerries M, Weichenhan D, Löffler E, Janssen PM, Eckhart AD, Martini J, Williams ML, Katus HA, Remppis A, Koch WJ (2004) Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. J Clin Invest 114:1550–1563PubMedPubMedCentralGoogle Scholar
  57. 57.
    Most P, Seifert H, Gao E, Funakoshi H, Völkers M, Heierhorst J, Remppis A, Pleger ST, DeGeorge BR Jr, Eckhart AD, Feldman AM, Koch WJ (2006) Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation 114:1258–1268PubMedGoogle Scholar
  58. 58.
    Treves S, Scutari E, Robert M, Groh S, Ottolia M, Prestipino G, Ronjat M, Zorzato F (1997) Interaction of S100A1 with the Ca2+ release channel (ryanodine receptor) of skeletal muscle. Biochemistry 36:11496–11503PubMedGoogle Scholar
  59. 59.
    Prosser BL, Wright NT, Hernãndez-Ochoa EO, Varney KM, Liu Y, Olojo RO, Zimmer DB, Weber DJ, Schneider MF (2008) S100A1 binds to the calmodulin-binding site of ryanodine receptor and modulates skeletal muscle excitation-contraction coupling. J Biol Chem 283:5046–5057PubMedGoogle Scholar
  60. 60.
    Prosser BL, Hernández-Ochoa EO, Zimmer DB, Schneider MF (2009) The Qγ component of intra-membrane charge movement is present in mammalian muscle fibres, but suppressed in the absence of S100A1. J Physiol 587:4523–4541PubMedPubMedCentralGoogle Scholar
  61. 61.
    Heierhorst J, Kobe B, Feil SC, Parker MW, Benian GM, Weiss KR, Kemp BE (1996) Ca2+/S100 regulation of giant protein kinases. Nature 380:636–639PubMedGoogle Scholar
  62. 62.
    Yamasaki R, Berri M, Wu Y, Trombitás K, McNabb M, Kellermayer MS, Witt C, Labeit D, Labeit S, Greaser M, Granzier H (2001) Titin-actin interaction in mouse myocardium: passive tension modulation and its regulation by calcium/S100A1. Biophys J 81:2297–2313PubMedPubMedCentralGoogle Scholar
  63. 63.
    Völkers M, Rohde D, Goodman C, Most P (2010) S100A1: a regulator of striated muscle sarcoplasmic reticulum Ca2+ handling, sarcomeric, and mitochondrial function. J Biomed Biotechnol 2010:178614PubMedPubMedCentralGoogle Scholar
  64. 64.
    Rambotti MG, Giambanco I, Spreca A, Donato R (1999) S100B and S100A1 proteins in bovine retina: their calcium-dependent stimulation of a membrane-bound guanylate cyclase activity as investigated by ultracytochemistry. Neuroscience 92:1089–1101PubMedGoogle Scholar
  65. 65.
    Kato K, Suzuki F, Ogasawara N (1988) Induction of S100 protein in 3T3-L1 cells during differentiation to adipocytes and its liberating by lipolytic hormones. Eur J Biochem 177:461–466PubMedGoogle Scholar
  66. 66.
    Cinti S, Cigolini M, Morroni M, Zingaretti MC (1989) S-100 protein in white preadipocytes: an immunoelectronmicroscopic study. Anat Rec 224:466–472PubMedGoogle Scholar
  67. 67.
    Zoico E, Di Francesco V, Olioso D, Fratta Pasini AM, Sepe A, Bosello O, Cinti S, Cominacini L, Zamboni M (2010) In vitro aging of 3T3-L1 mouse adipocytes leads to altered metabolism and response to inflammation. Biogerontology 11:111–122PubMedGoogle Scholar
  68. 68.
    Grum-Schwensen B, Klingelhofer J, Berg CH, El-Naaman C, Grigorian M, Lukanidin E, Ambartsumian N (2005) Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene. Cancer Res 65:3772–3780PubMedGoogle Scholar
  69. 69.
    Dmytriyeva O, Pankratova S, Owczarek S, Sonn K, Soroka V, Ridley CM, Marsolais A, Lopez-Hoyos M, Ambartsumian N, Lukanidin E, Bock E, Berezin V, Kiryushko D (2012) The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. Nat Commun 3:1197PubMedGoogle Scholar
  70. 70.
    Pankratova S, Klingelhofer J, Dmytriyeva O, Owczarek S, Renziehausen A, Syed N, Porter AE, Dexter DT, Kiryushko D (2018) The S100A4 protein signals through the ErbB4 receptor to promote neuronal survival. Theranostics 8:3977–3990PubMedPubMedCentralGoogle Scholar
  71. 71.
    Arner P, Petrus P, Esteve D, Boulomié A, Näslund E, Thorell A, Gao H, Dahlman I, Rydén M (2018) Screening of potential adipokines identifies S100A4 as a marker of pernicious adipose tissue and insulin resistance. Int J Obes (Lond) 42:2047–2056Google Scholar
  72. 72.
    EL Naaman C, Grum-Schwensen B, Mansouri A, Grigorian M, Santoni-Rugiu E, Hansen T, Kriajevska M, Schafer BW, Heizmann CW, Lukanidin E, Ambartsumian N (2004) Cancer predisposition in mice deficient for the metastasis-associated Mts1(S100A4) gene. Oncogene 23:3670–3680Google Scholar
  73. 73.
    Davies MP, Rudland PS, Robertson L, Parry EW, Jolicoeur P, Barraclough R (1996) Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours. Oncogene 13:1631–1637PubMedGoogle Scholar
  74. 74.
    Hou S, Jiao Y, Yuan Q, Zhai J, Tian T, Sun K, Chen Z, Wu Z, Zhang J (2018) S100A4 protects mice from high-fat diet-induced obesity and inflammation. Lab Invest 98:1025–1038PubMedGoogle Scholar
  75. 75.
    Kiryushko D, Novitskaya V, Soroka V, Klingelhofer J, Lukanidin E, Berezin V, Bock E (2006) Molecular mechanisms of Ca2+ signaling in neurons induced by the S100A4 protein. Mol Cell Biol 26:3625–3638PubMedPubMedCentralGoogle Scholar
  76. 76.
    Klingelhöfer J, Møller HD, Sumer EU, Sumer EU, Berg CH, Poulsen M, Kiryushko D, Soroka V, Ambartsumian N, Grigorian M, Lukanidin EM (2009) Epidermal growth factor receptor ligands as new extracellular targets for the metastasis-promoting S100A4 protein. FEBS J 276:5936–5948PubMedGoogle Scholar
  77. 77.
    Zhang R, Gao Y, Zhao X, Gao M, Wu Y, Han Y, Qiao Y, Luo Z, Yang L, Chen J, Ge G (2018) FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis. PLoS Biol 16:e2001493PubMedPubMedCentralGoogle Scholar
  78. 78.
    Schiopu A, Cotoi OS (2013) S100A8 and S100A9: DAMPs at the crossroads between innate immunity, traditional risk factors, and cardiovascular disease. Mediat Inflamm 2013:828354Google Scholar
  79. 79.
    Mortensen OH, Nielsen AR, Erikstrup C, Plomgaard P, Fischer CP, Krogh-Madsen R, Lindegaard B, Petersen AM, Taudorf S, Pedersen BK (2009) Calprotectin: a novel marker of obesity. PLoS One 4:e7419PubMedPubMedCentralGoogle Scholar
  80. 80.
    Catalán V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Rotellar F, Valentí V, Silva C, Gil MJ, Fernández-Real JM, Salvador J, Frühbeck G (2011) Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss. Mol Med 17:1157–1167PubMedPubMedCentralGoogle Scholar
  81. 81.
    Sekimoto R, Kishida K, Nakatsuji H, Nakagawa T, Funahashi T, Shimomura I (2012) High circulating levels of S100A8/A9 complex (calprotectin) in male Japanese with abdominal adiposity and dysregulated expression of S100A8 and S100A9 in adipose tissues of obese mice. Biochem Biophys Res Commun 419:782–789PubMedGoogle Scholar
  82. 82.
    Yamaoka M, Maeda N, Nakamura S, Mori T, Inoue K, Matsuda K, Sekimoto R, Kashine S, Nakagawa Y, Tsushima Y, Fujishima Y, Komura N, Hirata A, Nishizawa H, Matsuzawa Y, Matsubara K, Funahashi T, Shimomura I (2013) Gene expression levels of S100 protein family in blood cells are associated with insulin resistance and inflammation (Peripheral blood S100 mRNAs and metabolic syndrome). Biochem Biophys Res Commun 433:450–455PubMedGoogle Scholar
  83. 83.
    Sekimoto R, Fukuda S, Maeda N, Tsushima Y, Matsuda K, Mori T, Nakatsuji H, Nishizawa H, Kishida K, Kikuta J, Maijima Y, Funahashi T, Ishii M, Shimomura I (2015) Visualized macrophage dynamics and significance of S100A8 in obese fat. Proc Natl Acad Sci USA 112:E2058–E2066PubMedGoogle Scholar
  84. 84.
    Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, Ramkhelawon B, Distel E, Westerterp M, Huang LS, Schmidt AM, Orchard TJ, Fisher EA, Tall AR, Goldberg IJ (2013) Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab 17:695–708PubMedPubMedCentralGoogle Scholar
  85. 85.
    Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, Dragoljevic D, Hong ES, Abdel-Latif A, Smyth SS, Choi SH, Korner J, Bornfeldt KE, Fisher EA, Dixit VD, Tall AR, Goldberg IJ, Murphy AJ (2014) Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab 19:821–835PubMedPubMedCentralGoogle Scholar
  86. 86.
    Shah RD, Xue C, Zhang H, Tuteja S, Li M, Reilly MP, Ferguson JF (2017) Expression of calgranulin genes S100A8, S100A9 and S100A12 is modulated by n-3 PUFA during inflammation in adipose tissue and mononuclear cells. PLoS One 12:e0169614PubMedPubMedCentralGoogle Scholar
  87. 87.
    Kromhout D, Bosschieter EB, de Lezenne Coulander C (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 312:1205–1209PubMedGoogle Scholar
  88. 88.
    Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (2006) n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 84:5–17PubMedGoogle Scholar
  89. 89.
    Mantelmacher FD, Zvibel I, Cohen K, Epshtein A, Pasmanik-Chor M, Vogl T, Kuperman Y, Weiss S, Drucker DJ, Varol C, Fishman S (2018) GIP regulates inflammation and body weight by restraining myeloid-cell-derived S100A8/A9. Nat Metab 1:58–69Google Scholar
  90. 90.
    Kerkhoff C, Klempt M, Kaever V, Sorg C (1999) The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabolism of arachidonic acid in human neutrophils. J Biol Chem 274:32672–32679PubMedGoogle Scholar
  91. 91.
    Yip RG, Boylan MO, Kieffer TJ, Wolfe MM (1998) Functional GIP receptors are present on adipocytes. Endocrinology 139:4004–4007PubMedGoogle Scholar
  92. 92.
    Nyberg J, Jacobsson C, Anderson MF, Eriksson PS (2007) Immunohistochemical distribution of glucose dependent insulinotropic polypeptide in the adult rat brain. J Neurosci Res 85:2099–2119PubMedGoogle Scholar
  93. 93.
    Kim SJ, Nian C, Karunakaran S, Clee SM, Isales CM, McIntosh CH (2012) GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PLoS One 7:e40156PubMedPubMedCentralGoogle Scholar
  94. 94.
    Varol C, Zvibel I, Spektor L, Mantelmacher FD, Vugman M, Thurm T, Khatib M, Elmaliah E, Halpern Z, Fishman S (2014) Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation. J Immunol 193:4002–4009PubMedGoogle Scholar
  95. 95.
    Liu Y, Zhang R, Xin J, Sun Y, Li J, Wei D, Zhao AZ (2011) Identification of S100A16 as a novel adipogenesis promoting factor in 3T3-L1 cells. Endocrinology 152:903–911PubMedGoogle Scholar
  96. 96.
    Inoue N, Yahagi N, Yamamoto T, Ishikawa M, Watanabe K, Matsuzaka T, Nakagawa Y, Takeuchi Y, Kobayashi K, Takahashi A, Suzuki H, Hasty AH, Toyoshima H, Yamada N, Shimano H (2008) Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance. J Biol Chem 283:21220–21229PubMedPubMedCentralGoogle Scholar
  97. 97.
    Zhang R, Su D, Zhu W, Huang Q, Liu M, Xue Y, Zhang Y, Li D, Zhao A, Liu Y (2014) Estrogen suppresses adipogenesis by inhibiting S100A16 expression. J Mol Endocrinol 52:235–244PubMedPubMedCentralGoogle Scholar
  98. 98.
    Li D, Zhang R, Zhu W, Xue Y, Zhang Y, Huang Q, Liu M, Liu Y (2013) S100A16 inhibits osteogenesis but stimulates adipogenesis. Mol Biol Rep 40:3465–3473PubMedGoogle Scholar
  99. 99.
    Zhang R, Zhu W, Du X, Xin J, Xue Y, Zhang Y, Li D, Liu Y (2012) S100A16 mediation of weight gain attenuation induced by dietary calcium. Metabolism 61:157–163PubMedGoogle Scholar
  100. 100.
    D’Amico F, Skarmoutsou E, Granata M, Trovato C, Rossi GA, Mazzarino MC (2016) S100A7: a rAMPing up AMP molecule in psoriasis. Cytokine Growth Factor Rev 32:97–104PubMedGoogle Scholar
  101. 101.
    Salama RH, Al-Shobaili HA, Al Robaee AA, Alzolibani AA (2013) Psoriasin: a novel marker linked obesity with psoriasis. Dis Markers 34:33–39PubMedGoogle Scholar
  102. 102.
    Sakurai M, Miki Y, Takagi K, Suzuki T, Ishida T, Ohuchi N, Sasano H (2017) Interaction with adipocyte stromal cells induces breast cancer malignancy via S100A7 upregulation in breast cancer microenvironment. Breast Cancer Res 19:70PubMedPubMedCentralGoogle Scholar
  103. 103.
    Vogl T, Pröpper C, Hartmann M, Strey A, Strupat K, van den Bos C, Sorg C, Roth J (1999) S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J Biol Chem 274:25291–25296PubMedGoogle Scholar
  104. 104.
    Hofmann Bowman M, Wilk J, Heydemann A, Kim G, Rehman J, Lodato JA, Raman J, McNally EM (2010) S100A12 mediates aortic wall remodeling and aortic aneurysm. Circ Res 106:145–154PubMedGoogle Scholar
  105. 105.
    Hofmann Bowman MA, Heydemann A, Gawdzik J, Shilling RA, Camoretti-Mercado B (2011) Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation. Clin Exp Allergy 41:878–889PubMedPubMedCentralGoogle Scholar
  106. 106.
    Yan WX, Armishaw C, Goyette J, Yang Z, Cai H, Alewood P, Geczy CL (2008) Mast cell and monocyte recruitment by S100A12 and its hinge domain. J Biol Chem 283:13035–13043PubMedGoogle Scholar
  107. 107.
    Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901PubMedGoogle Scholar
  108. 108.
    Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL (2007) S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol 119:106–114PubMedGoogle Scholar
  109. 109.
    Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, Tubaro C, Giambanco I (2009) S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta Mol Cell Res 1793:1008–1022Google Scholar
  110. 110.
    Tsoporis JN, Marks A, Haddad A, Dawood F, Liu PP, Parker TG (2005) S100B expression modulates left ventricular remodeling after myocardial infarction in mice. Circulation 111:598–606PubMedGoogle Scholar
  111. 111.
    McIlroy M, McCartan D, Early S, Gaora PO, Pennington S, Hill AD, Young LS (2010) Interaction of developmental transcription factor HOXC11 with steroid receptor coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer [corrected]. Cancer Res 70:1585–1594PubMedGoogle Scholar
  112. 112.
    Sorci G, Giovannini G, Riuzzi F, Bonifazi P, Zelante T, Zagarella S, Bistoni F, Donato R, Romani L (2011) The danger signal S100B integrates pathogen- and danger-sensing pathways to restrain inflammation. PLoS Pathog 7:e1001315PubMedPubMedCentralGoogle Scholar
  113. 113.
    Zhang L, Liu W, Alizadeh D, Zhao D, Farrukh O, Lin J, Badie SA, Badie B (2011) S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway. Glia 59:486–498PubMedGoogle Scholar
  114. 114.
    Riuzzi F, Beccafico S, Sagheddu R, Chiappalupi S, Giambanco I, Bereshchenko O, Riccardi C, Sorci G, Donato R (2017) Levels of S100B protein drive the reparative process in acute muscle injury and muscular dystrophy. Sci Rep 7:12537PubMedPubMedCentralGoogle Scholar
  115. 115.
    Riuzzi F, Sorci G, Donato R (2011) S100B protein regulates myoblast proliferation and differentiation by activating FGFR1 in a bFGFdependent manner. J Cell Sci 124:2389–2400PubMedGoogle Scholar
  116. 116.
    Michetti F, Dell’Anna E, Tiberio G, Cocchia D (1983) Immunochemical and immunocytochemical study of S-100 protein in rat adipocytes. Brain Res 262:352–356PubMedGoogle Scholar
  117. 117.
    Suzuki F, Kato K, Nakajima T (1984) Hormonal regulation of adipose S-100 protein release. J Neurochem 43:1336–1341PubMedGoogle Scholar
  118. 118.
    Suzuki F, Kato K (1985) Inhibition of adipose S-100 protein release by insulin. Biochim Biophys Acta 845:311–316PubMedGoogle Scholar
  119. 119.
    Netto CB, Conte S, Leite MC, Pires C, Martins TL, Vidal P, Benfato MS, Giugliani R, Gonçalves CA (2006) Serum S100B protein is increased in fasting rats. Arch Med Res 37:683–686PubMedGoogle Scholar
  120. 120.
    Holtkamp K, Bühren K, Ponath G, von Eiff C, Herpertz-Dahlmann B, Hebebrand J, Rothermundt M (2008) Serum levels of S100B are decreased in chronic starvation and normalize with weight gain. J Neural Transm (Vienna) 115:937–940Google Scholar
  121. 121.
    Li D, Li K, Chen G, Xia J, Yang T, Cai P, Yao C, Yang Y, Yan S, Zhang R, Chen H (2016) S100B suppresses the differentiation of C3H/10T1/2 murine embryonic mesenchymal cells into osteoblasts. Mol Med Rep 14:3878–3886PubMedGoogle Scholar
  122. 122.
    Lin J, Yang Q, Wilder PT, Carrier F, Weber DJ (2010) The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. J Biol Chem 285:27487–27498PubMedPubMedCentralGoogle Scholar
  123. 123.
    Esposito G, Capoccia E, Sarnelli G, Scuderi C, Cirillo C, Cuomo R, Steardo L (2012) The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice. J Neuroinflammation 9:277PubMedPubMedCentralGoogle Scholar
  124. 124.
    Capoccia E, Cirillo C, Marchetto A, Tiberi S, Sawikr Y, Pesce M, D’Alessandro A, Scuderi C, Sarnelli G, Cuomo R, Steardo L, Esposito G (2015) S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncol Lett 9:2864–2870PubMedPubMedCentralGoogle Scholar
  125. 125.
    Yang T, Cheng J, Yang Y, Qi W, Zhao Y, Long H, Xie R, Zhu B, S100B (2017) Mediates stemness of ovarian cancer stem-like cells through inhibiting p53. Stem Cells 35:325–336PubMedGoogle Scholar
  126. 126.
    Yang T, Cheng J, You J, Yan B, Liu H, Li F (2018) S100B promotes chemoresistance in ovarian cancer stem cells by regulating p53. Oncol Rep 40:1574–1582PubMedGoogle Scholar
  127. 127.
    Sorci G, Riuzzi F, Giambanco I, Donato R (2013) RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta Mol Cell Res 1833:101–109Google Scholar
  128. 128.
    Gaens KH, Stehouwer CD, Schalkwijk CG (2013) Advanced glycation endproducts and its receptor for advanced glycation endproducts in obesity. Curr Opin Lipidol 24:4–11PubMedGoogle Scholar
  129. 129.
    Boyer F, Vidot JB, Dubourg AG, Rondeau P, Essop MF, Bourdon E (2015) Oxidative stress and adipocyte biology: focus on the role of AGEs. Oxid Med Cell Longev 2015:534873PubMedPubMedCentralGoogle Scholar
  130. 130.
    Ramasamy R, Shekhtman A, Schmidt AM (2016) The multiple faces of RAGE-opportunities for therapeutic intervention in aging and chronic disease. Expert Opin Ther Targ 20:431–446Google Scholar
  131. 131.
    López-Díez R, Shekhtman A, Ramasamy R, Schmidt AM (2016) Cellular mechanisms and consequences of glycation in atherosclerosis and obesity. Biochim Biophys Acta 1862:2244–2252PubMedGoogle Scholar
  132. 132.
    Zhang J, Zhang L, Zhang S, Yu Q, Xiong F, Huang K, Wang CY, Yang P (2017) HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol 454:103–111PubMedGoogle Scholar
  133. 133.
    Steiner J, Schiltz K, Walter M, Wunderlich MT, Keilhoff G, Brisch R, Bielau H, Bernstein HG, Bogerts B, Schroeter ML, Westphal S (2010) S100B serum levels are closely correlated with body mass index: an important caveat in neuropsychiatric research. Psychoneuroendocrinology 35:321–324PubMedGoogle Scholar
  134. 134.
    Kheirouri S, Ebrahimi E, Alizadeh M (2018) Association of S100B serum levels with metabolic syndrome and its components. Acta Med Port 31:201–206PubMedGoogle Scholar
  135. 135.
    Monden M, Koyama H, Otsuka Y, Morioka T, Mori K, Shoji T, Mima Y, Motoyama K, Fukumoto S, Shioi A, Emoto M, Yamamoto Y, Yamamoto H, Nishizawa Y, Kurajoh M, Yamamoto T, Inaba M (2013) Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2. Diabetes 62:478–489PubMedPubMedCentralGoogle Scholar
  136. 136.
    Fujiya A, Nagasaki H, Seino Y, Okawa T, Kato J, Fukami A, Himeno T, Uenishi E, Tsunekawa S, Kamiya H, Nakamura J, Oiso Y, Hamada Y (2014) The role of S100B in the interaction between adipocytes and macrophages. Obesity (Silver Spring) 22:371–379Google Scholar
  137. 137.
    Buckman LB, Anderson-Baucum EK, Hasty AH, Ellacott KLJ (2014) Regulation of S100B in white adipose tissue by obesity in mice. Adipocyte 3:215–220PubMedPubMedCentralGoogle Scholar
  138. 138.
    Bowden-Davies K, Connolly J, Burghardt P, Koch LG, Britton SL, Burniston JG (2015) Label-free profiling of white adipose tissue of rats exhibiting high or low levels of intrinsic exercise capacity. Proteomics 15:2342–2349PubMedPubMedCentralGoogle Scholar
  139. 139.
    Son KH, Son M, Ahn H, Oh S, Yum Y, Choi CH, Park KY, Byun K (2016) Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat. Biochem Biophys Res Commun 477:271–276PubMedGoogle Scholar
  140. 140.
    Hosokawa K, Hamada Y, Fujiya A, Murase M, Maekawa R, Niwa Y, Izumoto T, Seino Y, Tsunekawa S, Arima H (2017) S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells. Am J Physiol Endocrinol Metab 312:E471–E481PubMedGoogle Scholar
  141. 141.
    Barbatelli G, Morroni M, Vinesi P, Cinti S, Michetti F (1993) S-100 protein in rat brown adipose tissue under different functional conditions: a morphological, immunocytochemical, and immunochemical study. Exp Cell Res 208:226–231PubMedGoogle Scholar
  142. 142.
    Zeng X, Ye M, Resch JM, Jedrychowski MP, Hu B, Lowell BB, Ginty DD, Spiegelman BM (2019) Innervation of thermogenic adipose tissue via a calsyntenin 3β–S100b axis. Nature.  https://doi.org/10.1038/s41586-019-1156-9 CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Huttunen HJ, Kuja-Panula J, Sorci G, Agneletti AL, Donato R, Rauvala H (2000) Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 275(51):40096–40105PubMedGoogle Scholar
  144. 144.
    Businaro R, Leone S, Fabrizi C, Sorci G, Donato R, Lauro GM, Fumagalli L (2006) S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses. J Neurosci Res 83:897–906PubMedGoogle Scholar
  145. 145.
    Morozzi G, Beccafico S, Bianchi R, Riuzzi F, Bellezza I, Giambanco I, Arcuri C, Minelli A, Donato R (2017) Oxidative stress-induced S100B accumulation converts myoblasts into brown adipocytes via an NF-κB/YY1/miR-133 axis and NF-κB/YY1/BMP-7 axis. Cell Death Differ 24:2077–2088PubMedPubMedCentralGoogle Scholar
  146. 146.
    Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM et al (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004PubMedPubMedCentralGoogle Scholar
  147. 147.
    Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M et al (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6:38–54PubMedPubMedCentralGoogle Scholar
  148. 148.
    Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S et al (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–967PubMedPubMedCentralGoogle Scholar
  149. 149.
    Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S (2017) Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle 8:349–369PubMedPubMedCentralGoogle Scholar
  150. 150.
    Bellezza I, Giambanco I, Minelli A, Donato R (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res 1865:721–733PubMedGoogle Scholar
  151. 151.
    Beccafico S, Riuzzi F, Puglielli C, Mancinelli R, Fulle S, Sorci G, Donato R (2011) Human muscle satellite cells show age-related differential expression of S100B protein and RAGE. Age (Dordr) 33:523–541Google Scholar
  152. 152.
    Asakura A, Komaki M, Rudnicki M (2001) Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation 68:245–253PubMedGoogle Scholar
  153. 153.
    Frühbeck G, Sesma P, Burrell MA (2009) PRDM16: the interconvertible adipo-myocyte switch. Trends Cell Biol 19:141–146PubMedGoogle Scholar
  154. 154.
    Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ, Cohen P, Frontini A, Bhowmick DC, Ye L, Cinti S, Spiegelman BM (2012) Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab 15:230–239PubMedPubMedCentralGoogle Scholar
  155. 155.
    Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A, Corvera S, Cinti S (2012) The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab 15:222–229PubMedPubMedCentralGoogle Scholar
  156. 156.
    Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97PubMedPubMedCentralGoogle Scholar
  157. 157.
    Giordano A, Frontini A, Cinti S (2016) Convertible visceral fat as a therapeutic target to curb obesity. Nat Rev Drug Discov 15:405–424PubMedGoogle Scholar
  158. 158.
    Wang W, Seale P (2016) Control of brown and beige fat development. Nat Rev Mol Cell Biol 17:691–702PubMedPubMedCentralGoogle Scholar
  159. 159.
    Vegiopoulos A, Müller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel Diaz M, Rozman J, Hrabe de Angelis M, Nüsing RM, Meyer CW, Wahli W, Klingenspor M, Herzig S (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328:1158–1161PubMedGoogle Scholar
  160. 160.
    Diaz MB, Herzig S, Vegiopoulos A (2014) Thermogenic adipocytes: from cells to physiology and medicine. Metabolism 63:1238–1249PubMedGoogle Scholar
  161. 161.
    Sidossis L, Kajimura S (2015) Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest 125:478–486PubMedPubMedCentralGoogle Scholar
  162. 162.
    Sidossis LS, Porter C, Saraf MK, Børsheim E, Radhakrishnan RS, Chao T, Ali A, Chondronikola M, Mlcak R, Finnerty CC, Hawkins HK, Toliver-Kinsky T, Herndon DN (2015) Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab 22:219–227PubMedPubMedCentralGoogle Scholar
  163. 163.
    Lee YH, Petkova AP, Granneman JG (2013) Identification of an adipogenic niche for adipose tissue remodeling and restoration. Cell Metab 18:355–367PubMedPubMedCentralGoogle Scholar
  164. 164.
    Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292–1308PubMedPubMedCentralGoogle Scholar
  165. 165.
    Babaei R, Schuster M, Meln I, Lerch S, Ghandour RA, Pisani DF, Bayindir-Buchhalter I, Marx J, Wu S, Schoiswohl G, Billeter AT, Krunic D, Mauer J, Lee YH, Granneman JG, Fischer L, Müller-Stich BP, Amri EZ, Kershaw EE, Heikenwälder M, Herzig S, Vegiopoulos A (2018) Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. Sci Signal 11:eaai7838PubMedGoogle Scholar
  166. 166.
    Jung N, Park S, Choi Y, Park JW, Hong YB, Park HH, Yu Y, Kwak G, Kim HS, Ryu KH, Kim JK, Jo I, Choi BO, Jung SC (2016) Tonsil-derived mesenchymal stem cells differentiate into a schwann cell phenotype and promote peripheral nerve regeneration. Int J Mol Sci 17(11):E1867PubMedGoogle Scholar
  167. 167.
    Xiao YZ, Wang S (2015) Differentiation of Schwann-like cells from human umbilical cord blood mesenchymal stem cells in vitro. Mol Med Rep 11:1146–1152PubMedGoogle Scholar
  168. 168.
    Garbuglia M, Verzini M, Giambanco I, Spreca A, Donato R (1996) Effects of calcium-binding proteins (S100a0, S100a, S100b) on desmin assembly in vitro. FASEB J 10:317–324PubMedGoogle Scholar
  169. 169.
    Sorci G, Agneletti AL, Donato R (2000) Effects of S100A1 and S100B on microtubule stability. An in vitro study using triton-cytoskeletons from astrocyte and myoblast cell lines. Neuroscience 99:773–783PubMedGoogle Scholar
  170. 170.
    Tubaro C, Arcuri C, Giambanco I, Donato R (2010) S100B protein in myoblasts modulates myogenic differentiation via NF-κB-dependent inhibition of MyoD expression. J Cell Physiol 223:270–282PubMedGoogle Scholar
  171. 171.
    Tubaro C, Arcuri C, Giambanco I, Donato R (2011) S100B in myoblasts regulates the transition from activation to quiescence and from quiescence to activation, and reduces apoptosis. Biochim Biophys Acta Mol Cell Res 1813:1092–1104Google Scholar
  172. 172.
    Cinti S (2018) Adipose Organ Development and Remodeling. Compr Physiol 8:1357–1431PubMedGoogle Scholar
  173. 173.
    Kotzbeck P, Giordano A, Mondini E, Murano I, Severi I, Venema W, Cecchini MP, Kershaw EE, Barbatelli G, Haemmerle G, Zechner R, Cinti S (2018) Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation. J Lipid Res 59:784–794PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Francesca Riuzzi
    • 1
    • 2
  • Sara Chiappalupi
    • 1
    • 2
  • Cataldo Arcuri
    • 1
  • Ileana Giambanco
    • 1
  • Guglielmo Sorci
    • 1
    • 2
    • 3
  • Rosario Donato
    • 1
    Email author
  1. 1.Department of Experimental Medicine, Perugia Medical SchoolUniversity of PerugiaPerugiaItaly
  2. 2.Interuniversity Institute of Myology (IIM)University of PerugiaPerugiaItaly
  3. 3.Centro Universitario di Ricerca sulla Genomica FunzionaleUniversity of PerugiaPerugiaItaly

Personalised recommendations