Markers of Adipogenesis, but Not Inflammation, in Adipose Tissue Are Independently Related to Insulin Sensitivity

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 8; pp. 3040 - 3049
• Main Authors: Matulewicz, Natalia, Stefanowicz, Magdalena, Nikołajuk, Agnieszka, Karczewska-Kupczewska, Monika
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.08.2017; Copyright Oxford University Press; Oxford University Press
• Subjects: Adipogenesis; Adipogenesis - genetics; Adiponectin - genetics; Adipose tissue; Adipose Tissue - immunology; Adipose Tissue - metabolism; Adult; Angiogenesis; Biomarkers - metabolism; Biopsy; Body fat; Body mass index; Body weight; Case-Control Studies; CCAAT-Enhancer-Binding Proteins - genetics; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Extracellular matrix; Extracellular Matrix - metabolism; Female; Gelatinase B; Gene expression; Glucose Clamp Technique; Glucose Transporter Type 4 - genetics; Humans; Inflammation; Insulin; Insulin Receptor Substrate Proteins - genetics; Insulin Resistance - genetics; JNK Mitogen-Activated Protein Kinases - genetics; Kinases; Leukocytes, Mononuclear; Macrophages; Male; Matrix Metalloproteinase 9 - genetics; Multiple regression analysis; NF-kappa B - genetics; NF-κB protein; Obesity; Obesity - genetics; Obesity - immunology; Obesity - metabolism; Overweight; Overweight - genetics; Overweight - immunology; Overweight - metabolism; Peripheral blood mononuclear cells; Polymerase chain reaction; Regression Analysis; Signal Transduction; Subcutaneous Fat - immunology; Subcutaneous Fat - metabolism; Transcription factors; Transcriptome; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2017-00597

ContextIn obesity, adipose tissue (AT) undergoes dynamic remodeling, including an alternation in adipogenesis, AT-resident cell content, angiogenesis, and turnover of extracellular matrix (ECM) components. Studies of AT in humans have been carried out mostly in people with severe metabolic abnormalities, like type 2 diabetes or morbid obesity.ObjectiveThe purpose of this study was to investigate subcutaneous AT gene expression of markers of adipogenesis, ECM remodeling, and inflammation in young, healthy, overweight or obese subjects.DesignThe study group comprised 83 normal-weight, 48 overweight, and 19 obese subjects. Euglycemic hyperinsulinemic clamp, biopsy of subcutaneous AT, and isolation of peripheral blood mononuclear cells (PBMCs) were performed. Gene expression was measured with real-time polymerase chain reaction.ResultsOverweight/obese subjects had lower AT expression of markers of adipogenesis, insulin signaling, and angiogenesis; higher expression of markers of ECM remodeling; altered expression of genes of the nuclear factor-κ-B (NFκB), but not c-Jun NH2-terminal kinase, pathway; and higher expression of macrophage markers but not markers of other immune cells. In multiple regression analysis, the expression of CEBPA, ADIPOQ, IRS1, IRS2, SLC2A4, and MMP9 was associated with insulin sensitivity independently of body mass index. No differences were found in inflammatory-gene PBMC expression.ConclusionOverweight/obesity is associated with altered expression of genes of adipogenesis, insulin signaling, ECM remodeling, and inflammation. NFκB seems to be the earliest inflammatory pathway altered at the transcriptional level in AT. Macrophages seem to be the first immune cells to infiltrate AT. Adipogenesis and ECM remodeling are the initial processes in AT that are independently associated with insulin sensitivity.Adipogenesis and extracellular matrix remodeling, but not inflammation, are the initial processes in adipose tissue that are independently associated with insulin sensitivity in young healthy humans.