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Review
. 2020 Jul 17;477(13):2509-2541.
doi: 10.1042/BCJ20190462.

Identification and characterization of adipose surface epitopes

Yasuhiro Onogi #  1   2 , Ahmed Elagamy Mohamed Mahmoud Khalil #  1   2 , Siegfried Ussar  1   2   3
Affiliations
Review

Identification and characterization of adipose surface epitopes

Yasuhiro Onogi et al. Biochem J. .

Abstract

Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. However, targeting individual cell surface proteins in adipocytes has been difficult due to important functions of these proteins outside adipose tissue, raising various safety concerns. Thus, one of the biggest challenges is the lack of adipose selective surface proteins and/or targeting reagents. Here, we discuss several receptor families with an important function in adipogenesis and mature adipocytes to highlight the complexity at the cell surface and illustrate the problems with identifying adipose selective proteins. We then discuss that, while no unique adipocyte surface protein might exist, how splicing, posttranslational modifications as well as protein/protein interactions can create enormous diversity at the cell surface that vastly expands the space of potentially unique epitopes and how these selective epitopes can be identified and targeted.

Keywords: adipogenesis; brown adipose tissue; insulin resistance; obesity; surface markers; white adipose tissue.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. Receptor families expressed on adipocytes.
TKR, tyrosine kinase receptor; TKAR, tyrosine kinase-associated receptor; Ser/ThrKR, serine/threonine kinase receptor; GLP-1, Glucagen-like peptide 1; GIPR, Glucose-dependent insulinotropic polypeptide receptor; GPR, G protein-coupled receptor; IR, insulin receptor; IGF1R, insulin-like growth factor 1 receptor; PDGFRs, platelet-derived growth factor receptors; FGFRs, fibroblast growth factor receptors; TNFR, tumor necrosis factor receptor; TGFBR, transforming growth factor beta receptor; TRPV1, transient receptor potential vanilloid type 1 channel; CIC3, chloride channel 3; P2X7R, ionotropic purinergic receptor 7; GLUT4, glucose transporter 4.
Figure 2.
Figure 2.. Receptors regulating pre- and mature adipocytes function.
Right side: receptors involved in preadipocyte differentiation. Left side: receptors promoting glucose uptake, thermogenesis, lipolysis and lipogenesis in mature adipocytes. IR, insulin receptor; IGF1R, insulin-like growth factor receptor; βAR, beta adrenergic receptor; AR, adenosine receptor; TGFBR, transforming growth factor beta receptor; P2YR, metabotropic purinergic receptor; P2XR, ionotropic purinergic receptor; FZDR, frizzled receptor; TNFR1, tumor necrosis factor alpha receptor 1; GLP1R, glucagon-like peptide-1 receptor; GIPR, glucose-dependent insulinotropic peptide receptor; CXCR2, CXC chemokine receptor 2; TPRV1, transient receptor potential vanilloid type-1; Pref1, preadipocyte factor 1; EP, prostaglandin E2 receptor; FP, prostaglandin F receptor; IP, prostaglandin I2 receptor; DP2, prostaglandin D2 receptor 2; GLUT4, glucose transporter type 4; BMP, bone morphogenetic protein; GDF, growth differentiation factor; TNF-α, tumor necrosis factor alpha; TGF-β, transforming growth factor beta; GLP-1, Glucagon-like peptide-1.
Figure 3.
Figure 3.. Extending cell surface epitope complexity beyond protein expression.
Diversity in cell surface epitopes is created through combination of protein expression and protein/protein interactions. Additional diversity in cell surface epitopes is achieved through posttranscriptional and posttranslational modifications. Splicing can be tissue and/or cell type specific. Proteolysis can generate tissue-specific fragments from ubiquitously expressed proteins. Glycosylation is one representative for posttranslational modifications further increasing surfome diversity.
Figure 4.
Figure 4.. Approaches for identification and characterization of cell surface epitopes.
(A,B) Indirect approaches to identify the cell surface epitopes. (A) Transcriptomics can provide information to predict potential unique epitopes and splice variants. (B) Proteomics identifies protein complexes and posttranslational modifications as well as splice variants. (C) Approaches capable of not only identifying but also targeting adipocyte selective epitopes. Antibodies, peptides and aptamers can all recognize epitopes of unknown proteins and protein complexes in addition to known proteins. These high affinity molecules are obtained by enrichment from large libraries screened with in vitro and in vivo methods. scFv, single-chain variable fragments; sdAb, single-domain antibody.
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References

    1. Coelho M., Oliveira T. and Fernandes R. (2013) Biochemistry of adipose tissue: an endocrine organ. Arch. Med. Sci. 9, 191–200 10.5114/aoms.2013.33181 - DOI - PMC - PubMed
    1. Schoettl T., Fischer I.P. and Ussar S. (2018) Heterogeneity of adipose tissue in development and metabolic function. J. Exp. Biol. 221, jeb162958 10.1242/jeb.162958 - DOI - PubMed
    1. Ikeda K., Maretich P. and Kajimura S. (2018) The common and distinct features of brown and beige adipocytes. Trends Endocrinol. Metab. 29, 191–200 10.1016/j.tem.2018.01.001 - DOI - PMC - PubMed
    1. Bachman E.S., Dhillon H., Zhang C.Y., Cinti S., Bianco A.C., Kobilka B.K. et al. (2002) betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297, 843–845 10.1126/science.1073160 - DOI - PubMed
    1. Wang Q.A., Tao C., Gupta R.K. and Scherer P.E. (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat. Med. 19, 1338–1344 10.1038/nm.3324 - DOI - PMC - PubMed

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