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

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 regu...

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Autores principales: Baker, Nicki A., Muir, Lindsey A., Washabaugh, Alexandra R., Neeley, Christopher K., Chen, Sophie Yu-Pu, Flesher, Carmen G., Vorwald, John, Finks, Jonathan F., Ghaferi, Amir A., Mulholland, Michael W., Varban, Oliver A., Lumeng, Carey N., O’Rourke, Robert W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460687/
https://www.ncbi.nlm.nih.gov/pubmed/28359093
http://dx.doi.org/10.1210/jc.2016-2915
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author Baker, Nicki A.
Muir, Lindsey A.
Washabaugh, Alexandra R.
Neeley, Christopher K.
Chen, Sophie Yu-Pu
Flesher, Carmen G.
Vorwald, John
Finks, Jonathan F.
Ghaferi, Amir A.
Mulholland, Michael W.
Varban, Oliver A.
Lumeng, Carey N.
O’Rourke, Robert W.
author_facet Baker, Nicki A.
Muir, Lindsey A.
Washabaugh, Alexandra R.
Neeley, Christopher K.
Chen, Sophie Yu-Pu
Flesher, Carmen G.
Vorwald, John
Finks, Jonathan F.
Ghaferi, Amir A.
Mulholland, Michael W.
Varban, Oliver A.
Lumeng, Carey N.
O’Rourke, Robert W.
author_sort Baker, Nicki A.
collection PubMed
description 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.
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spelling pubmed-54606872018-03-01 Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix Baker, Nicki A. Muir, Lindsey A. Washabaugh, Alexandra R. Neeley, Christopher K. Chen, Sophie Yu-Pu Flesher, Carmen G. Vorwald, John Finks, Jonathan F. Ghaferi, Amir A. Mulholland, Michael W. Varban, Oliver A. Lumeng, Carey N. O’Rourke, Robert W. J Clin Endocrinol Metab Clinical Research Articles 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. Endocrine Society 2017-01-05 /pmc/articles/PMC5460687/ /pubmed/28359093 http://dx.doi.org/10.1210/jc.2016-2915 Text en
spellingShingle Clinical Research Articles
Baker, Nicki A.
Muir, Lindsey A.
Washabaugh, Alexandra R.
Neeley, Christopher K.
Chen, Sophie Yu-Pu
Flesher, Carmen G.
Vorwald, John
Finks, Jonathan F.
Ghaferi, Amir A.
Mulholland, Michael W.
Varban, Oliver A.
Lumeng, Carey N.
O’Rourke, Robert W.
Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title_full Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title_fullStr Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title_full_unstemmed Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title_short Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix
title_sort diabetes-specific regulation of adipocyte metabolism by the adipose tissue extracellular matrix
topic Clinical Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460687/
https://www.ncbi.nlm.nih.gov/pubmed/28359093
http://dx.doi.org/10.1210/jc.2016-2915
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