Adipose tissue collagen VI in obesity.

Abstract

OBJECTIVES:

Basic science studies show that the extracellular matrix of adipose tissue, mainly represented by collagen VI, is dysfunctional in obesity and contributes to the development of the metabolic syndrome. We hypothesized in humans that increased collagen VI alpha3-subunit (COL6A3) mRNA is associated with adipose tissue macrophage chemotaxis and inflammation and that weight gain is accompanied by changes in the expression of COL6A3.

RESEARCH DESIGN AND METHODS:

Adipose tissue biopsies were obtained from a cross-sectional study (n = 109), an overfeeding study (n = 9), and a pioglitazone treatment study (n = 14). Adipose tissue gene expression was measured by quantitative RT-PCR, immunohistochemistry, and adipocyte sizing by fixation with osmium and Coulter counting. Body composition was measured by dual-energy x-ray absorptiometry and visceral adipose tissue by computed tomography. Patients with high or low COL6A3 mRNA were compared by one-way ANOVA.

RESULTS:

In humans, immunohistochemistry revealed that COL6 is present in adipose tissue extracellular matrix. COL6A3 mRNA is correlated with body mass index (r = 0.60, P < 0.0001) and fat mass (r = 0.41, P < 0.0001). COL6A3 expression was similar in obese vs. type 2 diabetes patients. Obese subjects with high COL6A3 mRNA had greater visceral adipose tissue mass (P < 0.05), lower size of small and medium adipocytes (P < 0.05), more CD68+ and CD163/MAC2+ macrophages, and increased macrophage inflammatory protein-1alpha and macrophage chemoattractant protein-1alpha mRNA (P < 0.05). Eight weeks of overfeeding increased body weight and COL6A3 mRNA (P < 0.05). Pioglitazone decreased COL6A3 mRNA, and the change was inversely proportional to baseline COL6A3 mRNA (r = -0.95, P < 0.0001).

CONCLUSION:

These results are consistent with basic science data, suggesting that COL6A3 might contribute to adipose tissue inflammation.

• Authors: Magdalena Pasarica, Barbara Gowronska-Kozak, David Burk, Isabel Remedios, David Hymel, Jeff Gimble, Eric Ravussin, George A Bray, Steven R Smith
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 94 Issue 12 Pg. 5155-62 (Dec 2009) ISSN: 1945-7197 [Electronic] United States
• PMID: 19837927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• Collagen Type VI
• Hypoglycemic Agents
• RNA, Messenger
• Thiazolidinediones
• Pioglitazone

Topics

• Adipocytes (physiology, ultrastructure)
• Adipose Tissue (metabolism)
• Adolescent
• Adult
• Antigens, CD (biosynthesis)
• Antigens, Differentiation, Myelomonocytic (biosynthesis)
• Body Composition (genetics)
• Body Mass Index
• Cell Size
• Chemotaxis, Leukocyte (physiology)
• Collagen Type VI (biosynthesis, genetics)
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (genetics, metabolism)
• Female
• Humans
• Hyperphagia (metabolism)
• Hypoglycemic Agents (therapeutic use)
• Immunohistochemistry
• Inflammation (metabolism, pathology)
• Macrophages (metabolism)
• Male
• Obesity (metabolism)
• Pioglitazone
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Thiazolidinediones (therapeutic use)
• Weight Gain (genetics)
• Young Adult