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

Authors: LACKEY, DENISE - University Of San Diego; BURK, DAVID - Pennington Biomedical Research Center; ALI, MOHAMED - University Of California; MOSTAEDI, ROUZBEH - University Of California; SMITH, WILLIAM - University Of California; PARK, JIYOUNG - University Of Texas Southwestern Medical Center; SCHERER, PHILIP - University Of Texas Southwestern Medical Center; Seay, Shundra; McCoin, Colin; BONALDO, PAOLO - University Of California; Adams, Sean

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2014
Publication Date: 12/3/2013
Citation: Lackey, D.E., Burk, D.H., Ali, M.R., Mostaedi, R., Smith, W., Park, J., Scherer, P.E., Seay, S., Mccoin, C.S., Bonaldo, P., Adams, S.H. 2013. Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity. American Journal of Physiology - Endocrinology and Metabolism. 306:E233-E246. DOI: 10.1152/ajpendo.00476.2013.

Interpretive Summary: The extracellular matrix (ECM) plays an important role in 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 places a strain on the ECM remodeling machinery, which may promote disordered ECM, altered tissue integrity, and could promote pro-inflammatory 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 3-D confocal imaging, using collagen VI knockout mice as a validation tool. These new methods, combined with comprehensive measurement of WAT ECM proteolytic enzymes, transcript and blood analyte analyses were used to identify unique patho-phenotypes of Metabolic Syndrome (MetS) and type 2 diabetes mellitus (T2DM) in obese women using multivariate statistical modeling (PLS-DA) and univariate comparisons to weight-matched healthy obese individuals. In addition to expected differences in inflammation and glycemic control, ~20 ECM-related factors including omental tensile strength, collagen and enzyme transcripts helped discriminate metabolically-compromised vs. healthy obesity. This indicates that WAT ECM physiology is intimately linked to metabolic health status in obese humans, and the studies provide new tools to explore this relationship in detail.

Technical Abstract: The extracellular matrix (ECM) plays an important role in 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 places a strain on the ECM remodeling machinery, which may promote disordered ECM, altered tissue integrity, and could promote pro-inflammatory 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 3-D confocal imaging, using collagen VI knockout mice as a validation tool. These new methods, combined with comprehensive measurement of WAT ECM proteolytic enzymes, transcript and blood analyte analyses were used to identify unique patho-phenotypes of Metabolic Syndrome (MetS) and type 2 diabetes mellitus (T2DM) in obese women using multivariate statistical modeling (PLS-DA) and univariate comparisons to weight-matched healthy obese individuals. In addition to expected differences in inflammation and glycemic control, ~20 ECM-related factors including omental tensile strength, collagen and enzyme transcripts helped discriminate metabolically-compromised vs. healthy obesity. This indicates that WAT ECM physiology is intimately linked to metabolic health status in obese humans, and the studies provide new tools to explore this relationship in detail.