Faculty Collaboration Database

Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix. J Clin Endocrinol Metab 2017 Mar 01;102(3):1032-1043

Date

03/31/2017

Pubmed ID

28359093

Pubmed Central ID

PMC5460687

DOI

10.1210/jc.2016-2915

Scopus ID

2-s2.0-85015162691 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

CONTEXT: The role of the extracellular matrix (ECM) in regulating adipocyte metabolism in the context of metabolic disease is poorly defined.

OBJECTIVE: The objective of this study was to define the metabolic phenotype of adipocytes associated with human diabetes (DM) and the role of the ECM in regulating adipocyte metabolism.

DESIGN: Adipose tissues from obese patients were studied in standard 2-dimensional (2D) cell culture and an in vitro model of decellularized adipose tissue ECM repopulated with human adipocytes, and results were correlated with DM status.

SETTING: This study was conducted at the Academic University Medical Center and Veteran's Administration Hospital.

PATIENTS: Seventy patients with morbid obesity undergoing bariatric surgery were included in the study.

INTERVENTIONS: Visceral and subcutaneous adipose tissues were collected at the time of bariatric surgery.

OUTCOME MEASURES: This study used metabolic assays for glucose uptake, lipolysis, and lipogenesis in adipocytes in 2D cell culture and 3-dimensional ECM culture.

RESULTS: Adipocytes from subjects with DM manifest decreased glucose uptake and decreased lipolysis in 2D culture. ECM supports differentiation of mature adipocytes and recapitulates DM-specific differences in adipocyte metabolism observed in 2D culture. ECM from subjects without DM partially rescues glucose uptake and lipolytic defects in adipocytes from subjects with DM, whereas ECM from subjects with DM impairs glucose uptake in adipocytes from subjects without DM.

CONCLUSIONS: DM is associated with adipocyte metabolic dysfunction. The ECM regulates adipocyte metabolism. Nondiabetic ECM rescues metabolic dysfunction in DM adipocytes, whereas DM ECM imparts features of metabolic dysfunction to nondiabetic adipocytes. These findings suggest the ECM as a target for manipulating adipose tissue metabolism.

Author List

Baker NA, Muir LA, Washabaugh AR, Neeley CK, Chen SY, Flesher CG, Vorwald J, Finks JF, Ghaferi AA, Mulholland MW, Varban OA, Lumeng CN, O'Rourke RW

Author

Amir Ghaferi MD President, Phys Enterprise & SAD Clinical Affairs in the Medical College Physicians Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Abdominal Fat
Adipocytes
Adult
Case-Control Studies
Cell Culture Techniques
Cell Differentiation
Collagen Type I
Diabetes Mellitus, Type 2
Extracellular Matrix
Female
Glucose
Humans
Immunohistochemistry
In Vitro Techniques
Intra-Abdominal Fat
Lipogenesis
Lipolysis
Male
Microscopy, Electron, Scanning
Middle Aged
Obesity
Real-Time Polymerase Chain Reaction
Subcutaneous Fat