Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity

• Published in: International Journal of Obesity Vol. 35; no. 9; pp. 1154 - 1164
• Main Authors: Tienen, F.H.J van, Kallen, C.J.H. van der, Lindsey, P.J, Wanders, R.J, Greevenbroek, M.M. van, Smeets, H.J.M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.2011; Nature Publishing Group UK
• Subjects: 631/136/142; 631/208/191/2018; 692/699/2743/137/773; 692/699/2743/393; Actin; Adipocytes; Adipocytes - pathology; adipogenesis; Adipogenesis - genetics; Adipose Tissue; Adipose Tissue - pathology; Age; Apoptosis; Biological and medical sciences; Biology; Biopsy; Body fat; Body Mass Index; Cell culture; Cell Differentiation; Cells, Cultured; Cytoskeleton; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Diagnosis; Differentiation; DNA microarrays; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Extracellular matrix; Female; Gene expression; Gene Expression Profiling; gene expression regulation; genes; Genetic aspects; genetics; Health Promotion and Disease Prevention; Humans; Inflammation; Insulin; Insulin resistance; Integrins; Internal Medicine; Lipid metabolism; Lipids; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Microarray Analysis; microarray technology; microfilaments; Middle Aged; noninsulin-dependent diabetes mellitus; Obesity; original-article; pathology; patients; Physiological aspects; Preadipocytes; Proteins; Public Health; subcutaneous fat; Transcription; Transcription, Genetic; Type 2 diabetes; Netherlands; United States > US; type 2 diabetes mellitus; microarray; adipogenesis; preadipocyte; gene expression; Endocrinopathy; Type 2 diabetes; Human; Adipocyte; Obesity; Nutrition; Nutrition disorder; Precursor cell; Metabolic diseases; Cell differentiation; Gene expression; Gene expression profile; Preadipocyte; Differentiation; Nutritional status
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2010.275

Objective: Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. In this study, we identified the underlying molecular processes in preadipocytes of T2DM patients, a characteristic for the development of T2DM. Design and Participants: Preadipocyte cell cultures were prepared from subcutaneous fat biopsies of seven T2DM patients (age 53+/-12 years; body mass index (BMI) 34+/-5 kg m-2) and nine control subjects (age 51+/-12 years; BMI 30+/-3 kg m-2). Microarray analysis was used to identify altered processes between the T2DM and control preadipocytes. Results: Gene expression profiling showed changed expression of transcription regulators involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were downregulated, and inflammation/apoptosis was upregulated in T2DM preadipocytes. Conclusion: Decreased expression of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.