title: Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity.
abstract: The extracellular matrix (ECM) 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 accommodate 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 weight-matched healthy obese individuals. In addition to the expected differences in inflammation and glycemic control, approximately 20 ECM-related 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.
authors.affiliation: Obesity and Metabolism Research Unit, US Department of Agriculture-Agricultural Research Service Western Human Nutrition Research Center, Davis, California;
authors.forename: Denise E
authors.initials: DE
authors.lastname: Lackey
authors.forename: David H
authors.initials: DH
authors.lastname: Burk
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Ali
authors.forename: Rouzbeh
authors.initials: R
authors.lastname: Mostaedi
authors.forename: William H
authors.initials: WH
authors.lastname: Smith
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Shundra A
authors.initials: SA
authors.lastname: Seay
authors.forename: Colin S
authors.initials: CS
authors.lastname: McCoin
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D052436:Adipose Tissue, White / Q000648:ultrastructure*; D000328:Adult; D000818:Animals; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013718:Tensile Strength; D055815:Young Adult
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI
keywords: adipose inflammation; bariatric surgery; extracellular matrix; matrix metalloproteinase; type 2 diabetes mellitus