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J Clin Endocrinol Metab. 2017 Mar 1;102(3):1032-1043. doi: 10.1210/jc.2016-2915.

Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix.

Author information

1
Department of Surgery.
2
Department of Pediatrics and Communicable Diseases.
3
Center for Statistical Consultation & Research and.
4
Undergraduate Research Opportunity Program, University of Michigan, Ann Arbor, Michigan 48109; and.
5
Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, Michigan 48109.
6
Graduate Program in Immunology, and.
7
Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109.

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.

PMID:
28359093
PMCID:
PMC5460687
DOI:
10.1210/jc.2016-2915
[Indexed for MEDLINE]
Free PMC Article

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