Adipocyte Extracellular Matrix Composition, Dynamics and Role in Obesity
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Cell. Mol. Life Sci. (2010) 67:1277–1292 DOI 10.1007/s00018-010-0263-4 Cellular and Molecular Life Sciences REVIEW Adipocyte extracellular matrix composition, dynamics and role in obesity Edwin C. M. Mariman • Ping Wang Received: 20 November 2009 / Revised: 5 January 2010 / Accepted: 7 January 2010 / Published online: 27 January 2010 Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract The central role of the adipose tissue in lipid physiologic role of the adipose tissue. The major functions metabolism places specific demands on the cell structure of of adipose tissue are: adipocytes. The protein composition and dynamics of the • site for energy storage extracellular matrix (ECM) is of crucial importance for the • endocrine/paracrine regulator of energy metabolism functioning of those cells. Adipogenesis is a bi-phasic • thermal insulation of the body process in which the ECM develops from a fibrillar to a • shock cushion to protect organs from mechanical laminar structure as cells move from the commitment damage phase to the growth phase characterized by storage of vast amounts of triglycerides. Mature adipocytes appear to Those functions place specific demands on the adipose spend a lot of energy on the maintenance of the ECM. tissue with respect to its structure and composition. Here, ECM remodeling is mediated by a balanced complement of we review various aspects of the adipocyte extracellular constructive and destructive enzymes together with their matrix (ECM) including its components, development, enhancers and inhibitors. ECM remodeling is an energy regulation, and relation to obesity. costing process regulated by insulin, by the energy Adipose tissue is histologically categorized as a type of metabolism, and by mechanical forces. In the obese, loose connective tissue and, as such, collagen contributes overgrowth of adipocytes may lead to instability of the considerably to the non-cell mass of this tissue. At least ECM, possibly mediated by hypoxia. partly, this collagen is produced by the adipocytes, but cells of the stromal vascular fraction containing preadipocytes, Keywords Adipocytes Á Extracellular matrix Á capillary endothelial cells, infiltrated monocytes/macro- Proteomics Á Dynamics Á Lipid metabolism Á Obesity Á phages, and a population of multipotent stem cells can also Hypoxia contribute to it. It was reported that each adipocyte is surrounded by a thick ECM referred to as basal lamina containing collagen IV as a major component [1]. This Introduction characteristic is shared with cells of bone and cartilage, which is not surprising since adipocytes, osteoblasts, and The global rise of overweight and obesity with the risk for chondrocytes are all of mesenchymal origin. However, complications like type II diabetes and cardiovascular while a strong ECM is the principal functional entity of disorders has intensified the attention on the metabolic and bone and cartilage, the basal lamina of adipose tissue may be more of a necessity for survival of the adipocytes. Mature human adipocytes store triglycerides in a single fat droplet that almost entirely fills the cell volume. Since only E. C. M. Mariman (&) Á P. Wang a lipid monolayer forms the boundary between stored fat Department of Human Biology, NUTRIM School for Nutrition, and cytosol, mechanical stress on such an organelle may Toxicology and Metabolism, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands easily lead to disruption. Transfer of mechanical stress e-mail: [email protected] from the outside to the inside of the cell can be decreased 1278 E. C. M. Mariman, P. Wang by the strong external skeleton. In addition, a strong have an extremely low abundance. With the emerging of extracellular scaffold can by linking the basal lamina of proteomics techniques, several studies of the adipocytes adipocytes diminish locally experienced mechanical stress secretome have been performed. From those, an impression by spreading forces over a larger area of the tissue. A can be obtained on the protein composition of the adipo- specific requirement of the ECM for cell survival indicates cyte ECM. Based on current literature [2–13], a list of core that the development of preadipocytes into fat-storing proteins annotated to be part of the adipocyte ECM is adipocytes should be accompanied by specific changes in shown in Table 1. This leaves out those proteins that are the make-up of the ECM. presently described as secreted or membrane proteins, some of which might interact with the ECM. Although there are a number of microarray studies on adipocytes, we Adipocyte ECM protein composition have exclusively focused on proteomics data to avoid possible discrepancies between mRNA and protein levels. Since the function of the ECM will depend on, and thus Altogether, 20 subunits of 12 different types of collagen will be reflected by, its molecular make-up, it is important have been identified from rodent cells, whereas subunits of to know which proteins have been identified so far as part collagens II, XI, and XXIII were not found with human of the adipocyte ECM. Overall, the ECM of adipocytes visceral adipocytes. This might suggest species- or fat seems composed of the same proteins as found in other cell depot-specific differences. However, the failure to detect a types. It is more the relative quantity in which those protein cannot be taken as proof of its absence, because the factors are combined that determines the cell-specificity of chance of detection depends on the biochemical charac- the ECM. Furthermore, this composition is related to the teristics of a protein, on experimental conditions, and on developmental stage, viability, and subtype of the employed proteomics techniques [14]. adipocytes. The two main classes of ECM proteins are Compared to other ECM components, collagen VI proteoglycans (Fig. 1) and fibrous proteins to which most seems more specific for adipocytes. It is highly enriched in published information is referring. adipocytes, and there is evidence of its contribution to the Early studies on the protein composition of the ECM pathology of obesity-related diseases [15, 16]. The pres- have used immunological techniques with or without pro- ence of all three subunits, a1(VI), a2(VI), and a3(VI), is tein labeling. In this way, Aratani and Kitagawa [2] required for the stable formation of collagen VI [17]. Using demonstrated the presence of collagen IV, laminin the yeast two-hybrid system, collagen VI was shown to be complexes, and nidogen (entactin) in the ECM of mouse able to strongly bind to collagen IV, an important com- 3T3-L1 adipocytes. In differentiated bovine intramuscular ponent of the basement membrane. Both collagens are preadipocytes (BIP), Nakajima et al. [3] showed the pres- classified as non-fibrillar types and their interaction has ence of type I–VI collagens, laminin and fibronectin, been suggested to mediate anchoring of the basement whereas based on staining, type II collagen was found to membrane to cells. Collagen VI has also been shown to Fig. 1 Visualization of the ECM of 3T3-L1 preadipocyte (a) and adipocytes (b)by immunohistological staining of heparin sulfate proteoglycan: green heparin sulfate proteoglycans stained by antibody (10E4 epitope; Seikagaku, Tokyo, Japan); red nuclear stained with propidium iodide. The fat droplets are visible as dark vesicles in the cytosol Adipocyte extracellular matrix Table 1 Core proteins annotated to be part of the ECM with evidence by proteomic studies (j) Gene name Symbol Human Human Mouse Mouse Rat WAT References visceral/ sub-cutaneous 3T3-L1/ 3T3-L1 primary omental adipose-derived F442A adiposomes adipocytes adipocytes cells adipocytes Agrecan 1 ACAN j [11] Basement membrane-specific heparan sulfate HSPG2 jjj[4, 8, 11, 13] proteoglycan core protein (HSPG) (perlecan) Betaglycan (transforming growth factor TGFBR3 jj[11] beta receptor III) Biglycan BGN j [9, 11] Calreticulin CALR jj j [4, 9, 10, 13] Cartilage intermediate layer protein CILP1 j [11] Chitinase-3-like protein 1 CHI3l1 jj[11, 13] Chondroitin sulfate proteoglycan 4 CSPG4 j [11] (NG2 proteoglycan) Coiled coil domain containing protein 80 CCDC80 j [13] Collagen a 1(I) chain COL1A1 jj jj [4, 6, 8–10, 13] Collagen a 2(I) chain COL1A2 jjj[4, 6, 8, 13] Collagen a 1(II) chain COL2A1 j [11] Collagen a 1(IIII) chain COL3A1 jj [4–6, 13] Collagen a 1(IV) chain COL4A1 jj[2, 6, 7] Collagen a 2(IV) chain COL4A2 jjj[2, 4, 6, 7, 9, 13] Collagen a 3(IV) chain COL4A3 j [11] Collagen a 5(IV) chain COL4A5 j [11] Collagen a 1(V) chain COL5A1 jj [6, 9, 13] Collagen a 2(V) chain COL5A2 j [7, 11] Collagen a 3(V) chain COL5A3 jj[11] Collagen a 1(VI) chain COL6A1 jjj[4–6, 8, 9, 13] Collagen a 2(VI) chain COL6A2 jjj[4–6, 8, 9, 13] Collagen a 3(VI) chain COL6A3 jjj[4, 5, 8, 13] Collagen a 1(XI) chain COL11A1 j [11] Collagen a 1(XII) chain COL12A1 jj[4, 11] Collagen a 1(XIV) chain (undulin) COL14A1 jj[4, 11, 13] Collagen a 1(XV) chain COL15A1 jjj[1, 9, 11, 13] Collagen a 1(XVIII) chain COL18A1 jj[4, 11, 13] Collagen a 1(XXIII) chain COL23A1 j [11] Connective tissue growth factor CTGF j [11] 1279 Decorin (bone proteoglycan II) DCN jj [11, 13] 1280 Table 1 continued Gene name Symbol Human Human Mouse Mouse Rat WAT References visceral/ sub-cutaneous 3T3-L1/ 3T3-L1 primary omental adipose-derived F442A adiposomes adipocytes adipocytes cells adipocytes Dermatopontin (tyrosine-rich acidic matrix protein;