Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Jun 9

PMID 32508807

Citations 26

Authors

Ariane R Pessentheiner

G Michelle Ducasa

Philip L S M Gordts

Affiliations

Soon will be listed here.

Abstract

Proteoglycans are a specific subset of glycoproteins found at the cell surface and in the extracellular matrix, where they interact with a plethora of proteins involved in metabolic homeostasis and meta-inflammation. Over the last decade, new insights have emerged on the mechanism and biological significance of these interactions in the context of diet-induced disorders such as obesity and type-2 diabetes. Complications of energy metabolism drive most diet-induced metabolic disorders, which results in low-grade chronic inflammation, thereby affecting proper function of many vital organs involved in energy homeostasis, such as the brain, liver, kidney, heart and adipose tissue. Here, we discuss how heparan, chondroitin and keratan sulfate proteoglycans modulate obesity-induced metabolic dysfunction and low-grade inflammation that impact the initiation and progression of obesity-associated morbidities.

Citing Articles

The role of the extracellular matrix in cardiac regeneration.

Wang X, Yu S, Xie L, Xiang M, Ma H Heliyon. 2025; 11(1):e41157.

PMID: 39834404 PMC: 11745795. DOI: 10.1016/j.heliyon.2024.e41157.

Exploring the Impact of Astaxanthin Supplementation in Conjunction with a 12-Week CrossFit Training Regimen on Selected Adipo-Myokines Levels in Obese Males.

Moqaddam M, Nemati M, Dara M, Hoteit M, Sadek Z, Ramezani A Nutrients. 2024; 16(17).

PMID: 39275173 PMC: 11397083. DOI: 10.3390/nu16172857.

Obesity-associated inflammatory macrophage polarization is inhibited by capsaicin and phytolignans.

Poynter M, Mank M, Ather J Am J Physiol Regul Integr Comp Physiol. 2024; 326(5):R370-R382.

PMID: 38436058 PMC: 11398870. DOI: 10.1152/ajpregu.00161.2023.

Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.

Hruska P, Kucera J, Kuruczova D, Buzga M, Pekar M, Holeczy P Am J Physiol Endocrinol Metab. 2023; 325(5):E562-E580.

PMID: 37792298 PMC: 10864023. DOI: 10.1152/ajpendo.00153.2023.

SubQ-Sim: A Subcutaneous Physiologically Based Biopharmaceutics Model. Part 1: The Injection and System Parameters.

Pepin X, Grant I, Wood J Pharm Res. 2023; 40(9):2195-2214.

PMID: 37634241 PMC: 10547635. DOI: 10.1007/s11095-023-03567-0.

References

Edwards I, Xu H, Wright M, Wagner W . Interleukin-1 upregulates decorin production by arterial smooth muscle cells. Arterioscler Thromb. 1994; 14(7):1032-9. DOI: 10.1161/01.atv.14.7.1032. View

Zhu H, Pan H, Cui Y, Wang X, Wang L, Li N . The changes of serum glypican4 in obese patients with different glucose metabolism status. J Clin Endocrinol Metab. 2014; 99(12):E2697-701. DOI: 10.1210/jc.2014-2018. View

Mauviel A, Santra M, Chen Y, Uitto J, Iozzo R . Transcriptional regulation of decorin gene expression. Induction by quiescence and repression by tumor necrosis factor-alpha. J Biol Chem. 1995; 270(19):11692-700. DOI: 10.1074/jbc.270.19.11692. View

Heisler L, Lam D . An appetite for life: brain regulation of hunger and satiety. Curr Opin Pharmacol. 2017; 37:100-106. DOI: 10.1016/j.coph.2017.09.002. View

Saltiel A, Olefsky J . Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017; 127(1):1-4. PMC: 5199709. DOI: 10.1172/JCI92035. View

Krauss R, La Belle M, Blanche P, Barrett P, Wight T, Chait A . ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan. J Lipid Res. 2002; 43(11):1969-77. DOI: 10.1194/jlr.m200322-jlr200. View

Mikami T, Kitagawa H . Biosynthesis and function of chondroitin sulfate. Biochim Biophys Acta. 2013; 1830(10):4719-33. DOI: 10.1016/j.bbagen.2013.06.006. View

Gotte M . Syndecans in inflammation. FASEB J. 2003; 17(6):575-91. DOI: 10.1096/fj.02-0739rev. View

Wellner M, Herse F, Janke J, Gorzelniak K, Engeli S, Bechart D . Endothelial cell specific molecule-1--a newly identified protein in adipocytes. Horm Metab Res. 2003; 35(4):217-21. DOI: 10.1055/s-2003-39477. View

10.

Stanford K, Bishop J, Foley E, Gonzales J, Niesman I, Witztum J . Syndecan-1 is the primary heparan sulfate proteoglycan mediating hepatic clearance of triglyceride-rich lipoproteins in mice. J Clin Invest. 2009; 119(11):3236-45. PMC: 2769193. DOI: 10.1172/JCI38251. View

11.

Ang X, Lee M, Blocki A, Chen C, Ong L, Asada H . Macromolecular crowding amplifies adipogenesis of human bone marrow-derived mesenchymal stem cells by enhancing the pro-adipogenic microenvironment. Tissue Eng Part A. 2013; 20(5-6):966-81. PMC: 3938936. DOI: 10.1089/ten.TEA.2013.0337. View

12.

Lim J, Sherling D, Teo C, Hausman D, Lin D, Wells L . Defining the regulated secreted proteome of rodent adipocytes upon the induction of insulin resistance. J Proteome Res. 2008; 7(3):1251-63. DOI: 10.1021/pr7006945. View

13.

Han J, Hiebert L . Alteration of endothelial proteoglycan and heparanase gene expression by high glucose, insulin and heparin. Vascul Pharmacol. 2013; 59(3-4):112-8. DOI: 10.1016/j.vph.2013.08.001. View

14.

Strader A, Reizes O, Woods S, Benoit S, Seeley R . Mice lacking the syndecan-3 gene are resistant to diet-induced obesity. J Clin Invest. 2004; 114(9):1354-60. PMC: 524223. DOI: 10.1172/JCI20631. View

15.

Williams K, Qiu G, Usui H, Dunn S, McCue P, Bottinger E . Decorin deficiency enhances progressive nephropathy in diabetic mice. Am J Pathol. 2007; 171(5):1441-50. PMC: 2043506. DOI: 10.2353/ajpath.2007.070079. View

16.

Mis E, Liem Jr K, Kong Y, Schwartz N, Domowicz M, Weatherbee S . Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length. Dev Biol. 2013; 385(1):67-82. PMC: 3895954. DOI: 10.1016/j.ydbio.2013.10.014. View

17.

Chitturi S, Abeygunasekera S, Farrell G, Holmes-Walker J, Hui J, Fung C . NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002; 35(2):373-9. DOI: 10.1053/jhep.2002.30692. View

18.

Gordts P, Esko J . Heparan sulfate proteoglycans fine-tune macrophage inflammation via IFN-β. Cytokine. 2015; 72(1):118-9. DOI: 10.1016/j.cyto.2014.12.013. View

19.

Morinaga H, Mayoral R, Heinrichsdorff J, Osborn O, Franck N, Hah N . Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice. Diabetes. 2014; 64(4):1120-30. PMC: 4375077. DOI: 10.2337/db14-1238. View

20.

Meissburger B, Perdikari A, Moest H, Muller S, Geiger M, Wolfrum C . Regulation of adipogenesis by paracrine factors from adipose stromal-vascular fraction - a link to fat depot-specific differences. Biochim Biophys Acta. 2016; 1861(9 Pt A):1121-1131. DOI: 10.1016/j.bbalip.2016.06.010. View