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


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.


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





Adipose tissue macrophage


Brown adipose tissue


Body mass index


Bone morphogenetic protein 7


Calsyntenin 3β


Damage-associated molecular pattern


Enteric endocrine cell


Glucose-dependent insulinotropic polypeptide


GIP receptor


Glucagon-like peptide-1


High-fat diet






Long-chain omega-3 polyunsaturated fatty acids




Receptor for advanced glycation endproducts


Ryanodine receptor


Stromal vascular fraction cell


Toll-like receptor


Tumor necrosis factor-α


Visceral adipose tissue


Uncoupling protein 1


White adipose tissue



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.


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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

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