Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance
- PMID: 21994960
- PMCID: PMC3232606
- DOI: 10.1210/jc.2011-1567
Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance
Abstract
Context: Insulin resistance is associated with inflammation, fibrosis, and hypoxia in adipose tissue.
Objective: This study was intended to better characterize the extracellular matrix (ECM) and vascularity of insulin-resistant adipose tissue.
Design: Adipose expression of collagens, elastin, and angiogenic factors was assessed using real-time RT-PCR and immunohistochemistry (IHC) in abdominal sc adipose tissue. Adipocyte-macrophage coculture experiments examined the effects of polarized macrophages on adipose ECM gene expression, and the effects of collagens were measured in an angiogenesis assay.
Participants and setting: A total of 74 nondiabetic subjects participated at a University Clinical Research Center.
Interventions: Interventions included baseline adipose biopsy and measurement of insulin sensitivity.
Main outcome measures: Outcome measures included characterization of vascularity and ECM in adipose tissue.
Results: CD31 (an endothelial marker) mRNA showed no significant correlation with body mass index or insulin sensitivity. In a subgroup of 17 subjects (nine obese, eight lean), CD31-positive capillary number in obese was decreased by 58%, whereas larger vessels were increased by 70%, accounting for the lack of change in CD31 expression with obesity. Using IHC, obese (compared with lean) subjects had decreased elastin and increased collagen V expression, and adipocytes cocultured with M2 macrophages had reduced elastin and increased collagen V expression. In obese subjects, collagen V was colocalized with large blood vessels, and the addition of collagen V to an angiogenesis assay inhibited endothelial budding.
Conclusions: The adipose tissue from obese/insulin-resistant subjects has fewer capillaries and more large vessels as compared with lean subjects. The ECM of adipose tissue may play an important role in regulating the expandability as well as angiogenesis of adipose tissue.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160001.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160002.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160003.gif)
![Fig. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160004.gif)
![Fig. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160005.gif)
![Fig. 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3232606/bin/zeg0121185160006.gif)
Similar articles
-
Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation.Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1016-27. doi: 10.1152/ajpendo.00329.2010. Epub 2010 Sep 14. Am J Physiol Endocrinol Metab. 2010. PMID: 20841504 Free PMC article.
-
Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects.J Clin Endocrinol Metab. 2016 Apr;101(4):1422-8. doi: 10.1210/jc.2015-4125. Epub 2016 Feb 12. J Clin Endocrinol Metab. 2016. PMID: 26871994 Free PMC article.
-
Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.PLoS One. 2014 Jul 10;9(7):e102190. doi: 10.1371/journal.pone.0102190. eCollection 2014. PLoS One. 2014. PMID: 25010722 Free PMC article.
-
Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases.Int J Mol Sci. 2019 Oct 2;20(19):4888. doi: 10.3390/ijms20194888. Int J Mol Sci. 2019. PMID: 31581657 Free PMC article. Review.
-
Adipose extracellular matrix remodelling in obesity and insulin resistance.Biochem Pharmacol. 2016 Nov 1;119:8-16. doi: 10.1016/j.bcp.2016.05.005. Epub 2016 May 12. Biochem Pharmacol. 2016. PMID: 27179976 Free PMC article. Review.
Cited by
-
Non-invasive optoacoustic imaging of dermal microcirculatory revascularization in diet-induced obese mice undergoing exercise intervention.Photoacoustics. 2024 Jun 30;38:100628. doi: 10.1016/j.pacs.2024.100628. eCollection 2024 Aug. Photoacoustics. 2024. PMID: 39055739 Free PMC article.
-
An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells.Int J Mol Sci. 2023 Dec 28;25(1):437. doi: 10.3390/ijms25010437. Int J Mol Sci. 2023. PMID: 38203607 Free PMC article.
-
Severity of adipose tissue dysfunction is associated with progression of pre-diabetes to type 2 diabetes: the Tehran Lipid and Glucose Study.BMC Public Health. 2024 Jan 9;24(1):121. doi: 10.1186/s12889-023-17381-1. BMC Public Health. 2024. PMID: 38191327 Free PMC article.
-
Childhood Obesity: Insight into Kidney Involvement.Int J Mol Sci. 2023 Dec 12;24(24):17400. doi: 10.3390/ijms242417400. Int J Mol Sci. 2023. PMID: 38139229 Free PMC article. Review.
-
White Adipose Tissue Heterogeneity in the Single-Cell Era: From Mice and Humans to Cattle.Biology (Basel). 2023 Sep 27;12(10):1289. doi: 10.3390/biology12101289. Biology (Basel). 2023. PMID: 37886999 Free PMC article. Review.
References
-
- Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP. 1993. Quantification of the relationship between insulin sensitivity and β-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42:1663–1672 - PubMed
-
- Suganami T, Ogawa Y. 2010. Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol 88:33–39 - PubMed
-
- Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, Kern EM, Nagarajan R, Spencer HJ, 3rd, Lee MJ, Fried SK, McGehee RE, Jr, Peterson CA, Kern PA. 2008. Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes 57:432–439 - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- UL1 TR000117/TR/NCATS NIH HHS/United States
- AG20941/AG/NIA NIH HHS/United States
- UL1 RR033173/RR/NCRR NIH HHS/United States
- DK80327/DK/NIDDK NIH HHS/United States
- R01 AG020941/AG/NIA NIH HHS/United States
- P20 RR021954-04/RR/NCRR NIH HHS/United States
- DK71349/DK/NIDDK NIH HHS/United States
- P20RR021954/RR/NCRR NIH HHS/United States
- 1UL1RR033173/RR/NCRR NIH HHS/United States
- 1UL1RR029884/RR/NCRR NIH HHS/United States
- UL1 TR001998/TR/NCATS NIH HHS/United States
- M01 RR014288/RR/NCRR NIH HHS/United States
- P20 RR021954/RR/NCRR NIH HHS/United States
- R01 DK071349/DK/NIDDK NIH HHS/United States
- UL1 RR029884/RR/NCRR NIH HHS/United States
- M01RR14288/RR/NCRR NIH HHS/United States
- R01 DK080327/DK/NIDDK NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical