Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity

Abstract

plays an important role in the maintenance of white adipose tissue (WAT) architecture and function, and proper ECM remodeling is critical to support WAT malleability to accomodate changes in energy storage needs. Obesity and adipocyte hypertrophy place a strain on the ECM remodeling machinery, which may promote disordered ECM and altered tissue integrity and could promote proinflammatory and cell stress signals. To explore these questions, new methods were developed to quantify omental and subcutaneous WAT tensile strength and WAT collagen content by three-dimensional confocal imaging, using collagen VI knockout mice as a methods validation tool. These methods, combined with comprehensive measurement of WAT ECM proteolytic enzymes, transcript, and blood analyte analyses, were used to identify unique pathophenotypes of metabolic syndrome and type 2 diabetes mellitus in obese women, using multivariate statistical modeling and univariate comparisons with weightmatched healthy obese individuals. In addition to the expected differences in inflammation and glycemic control, approximately 20 ECMrelated factors, including omental tensile strength, collagen, and enzyme transcripts, helped discriminate metabolically compromised obesity. This is consistent with the hypothesis that WAT ECM physiology is intimately linked to metabolic health in obese humans, and the studies provide new tools to explore this relationship. matrix metalloproteinase; bariatric surgery; adipose inflammation; type 2 diabetes mellitus; extracellular matrix WHITE ADIPOSE TISSUE (WAT) is the primary site of energy storage in humans and by its nature must be malleable to respond to changes in energy balance through expansion and contraction. Under healthy conditions, changes in WAT architecture and the extracellular matrix (ECM) are coordinated with alterations in adipocyte size to accommodate fat storage needs. In contrast, sustained excessive energy intake with concomitant development of hypertrophic adipocytes creates a strain on ECM adaptation with pathophysiological consequences such as inflammation and insulin resistance.Adipose transcript abundances of several ECM-related genes were increased in obese compared with nonobese human subjects, including cell adhesion molecules and ECM receptor interaction genes, whereas weight loss after gastric bypass surgery led to decreased expression of these genes (18). Collagen VI is enriched in adipose tissue, and visceral WAT mass is related to increased expression of collagen 6␣3 in humans and in genetically obese mice (21, 38). Some studies have indicated that, at least in severe obesity, WAT fibrosis is more prevalent compared with nonobese individuals and that fibrosis decreases with weight loss (13,14), and this is believed to play a role in obesity-associated inflammation. Genetically obese ob/ob mice deficient in collagen VI (and thus lower fibrosis) fed a high-fat diet have improved glucose tolerance, insulin signaling, and triglyceride disposal with greater adipocyte size along with reduced WAT inf...

Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue

“…2A). Intriguingly, type V collagens have been previously shown to induce proliferation and differentiation of preadipocytes in vitro (19,20) and regulate collagen fibrillogenesis to control ECM geometry and tensile strength (16,17), properties that have been implicated in metabolic dysfunction of obese AT (28). Immunofluorescence confirmed an increase in Col5 protein and revealed specific localization to vascular endothelial cells in plxnd1 mutant VAT (Fig.…”

“…To ascertain the architectural properties of ECM, we used the fluorescent collagen probe 5-(4,6-dichlorotriazinyl) aminofluorescein to label VAT-localized collagen fibers (SI Appendix, Fig. S9A) (28). ECM architecture of plxnd1 mutant VAT was markedly different from that of sibling VAT (Fig.…”

Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction

“…In bariatric surgery patients, no difference was noted in FCS of patients with or without the metabolic syndrome 25,66 . The first study assessed the metabolic syndrome on the basis of the Harmonized criteria 67 .…”

Role of Epicardial Fat to Buffer Deformation and Vibration in Coronary Arteries

“…40 Although epicardial fat might appear to be a flimsy wrapping material, adipose tissue has defined tensile strength and "toughness" which are due in large part to the extracellular matrix and collagen network surrounding the adipocytes. 43,44 Vibration dampening material, however, can be as seemingly flimsy as felt or as thin as tape. Vibration dampening materials have been the subject of many patents.…”