TABLE 1.
Overview of proteoglycans associated with phenotypes in the context of metabolic dysregulation and meta-inflammation.
| Proteoglycan | Core mass (kDa)a | Chain type (number)b | Subcellular localization | Phenotypic observations | |
| Humans | Relevant preclinical models | ||||
| Heparan sulfate proteoglycans | |||||
| Syndecan 1–4 (SDC1–4) | 31–45 | HS (2–3) in SDC2 and 4; HS/CS (3–4 HS/1-2 CS) in SDC1 and 3 | Membrane-bound | Plasma SDC1 correlates with T1D and DKD (77) and hypertriglyceridemia in T2D patients (84); SNP in SDC4 linked with predisposition to T2D and obesity (78, 79, 80) | Increased atherosclerosis in Apoe–/–Sdc1–/– mice (73); All SDCs: regulation of feeding behavior (89-92) |
| Glypican 1–6 (GPC 1–6) | 57–69 | HS (1–3) | Membrane-bound | Simpson-Golabi-Behmel syndrome (overgrowth) (GPC3-4) (98); GPC4 (serum, AT) increases with BMI, insulin resistance, NAFLD (100–106); GPC5 risk allele in DKD (107) | GPC5 correlates with DKD (108); |
| Perlecan (HSPG2) | ∼470 | HS (1–3) | Secreted/ECM | No data reported. | Obesity resistance in cartilage-rescued Hspg2–/– mice (109); Role in lipoprotein retention in atherosclerosis (113, 117, 118) |
| Chondroitin/Dermatan sulfate proteoglycans | |||||
| Endocan (ESM1) | 20 | DS (1) | Secreted | Serum and AT levels increase in obesity (126, 134, 135); T2D (128, 129); atherosclerosis (130); DKD (131, 135); NAFLD (132); and psoriasis (133) | Correlation with DKD (136) |
| Decorin (DCN) | 38–42 | DS/CS (1) | Secreted/ECM | Increased expression in AT in obesity and T2D (143, 149, 151); Upregulated in DKD (156) | Dcn–/– mice: increased obesity, AT inflammation, and glucose intolerance (151, 153); aggravated DKD (157) |
| Biglycan (BGN) | 38–42 | DS/CS (2) | Secreted/ECM | Upregulation in atherosclerotic plaques (166, 167); Increased in kidney injuries met with elevated inflammation, including DKD (171) | Bgn–/– mice: reduced AT inflammation upon obesity (160); overexpression in mice promotes atherosclerosis (166, 167); Bgn accumulates in glomeruli of DKD mice (170) |
| Keratan sulfate proteoglycans | |||||
| Lumican (LUM) | ∼37 | KS (1) | Secreted | Liver expression correlates with severity of NASH and NAFLD (174–176) | Lum–/– mice (females): increased obesity (177) |
| Osteoglycin (OGN) | 25–72 | KS and O-linked glycans | Secreted | OGN serum levels increase in response to weight loss in severely obese patients (184); Associated with atherosclerotic plaques (183) | Increased in atherosclerotic plaques in rabbits (182); Reduced levels of Ogn in obesity (185); Ogn–/– mice: glucose intolerance and insulin resistance in diet-induced obesity (185) |
AT, adipose tissue; HS, heparan sulfate; DS, dermatan sulfate; CS, chondroitin sulfate; ECM, extracellular matrix; T2D, type 2 diabetes; NASH, non-alcoholic steatohepatitis; NAFLD, non-alcoholic fatty liver disease; DKD, diabetic kidney disease. aVariation in core mass is due to species differences. bNumber of chains is based on the number of putative attachment sites for chain initiation as well as data from the literature; the actual number of chains varies by method, tissue, and species.