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S100 proteins in obesity: liaisons dangereuses

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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.

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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

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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.

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  1. Francesca Riuzzi and Sara Chiappalupi: Co-first authors.

  2. Guglielmo Sorci and Rosario Donato: Co-senior authors.

Authors and Affiliations

  1. Department of Experimental Medicine, Perugia Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy

    Francesca Riuzzi, Sara Chiappalupi, Cataldo Arcuri, Ileana Giambanco, Guglielmo Sorci & Rosario Donato

  2. Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy

    Francesca Riuzzi, Sara Chiappalupi & Guglielmo Sorci

  3. Centro Universitario di Ricerca sulla Genomica Funzionale, University of Perugia, 06132, Perugia, Italy

    Guglielmo Sorci

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Riuzzi, F., Chiappalupi, S., Arcuri, C. et al. S100 proteins in obesity: liaisons dangereuses. Cell. Mol. Life Sci. 77, 129–147 (2020). https://doi.org/10.1007/s00018-019-03257-4

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