Vascular reactivity contributes to adipose tissue remodeling in obesity

in Journal of Endocrinology
Authors:
Hye-Jin Lee BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea

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https://orcid.org/0000-0002-7800-7101
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Haifei Shi Department of Biology, Miami University, Oxford, Ohio, USA

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Hella S Brönneke Max Planck Institute for Metabolism Research, Köln, Germany

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Bo-Yeong Jin BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea

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Sang-Hyun Choi Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea

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Randy J Seeley Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA

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Dong-Hoon Kim BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea

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Correspondence should be addressed to D-H Kim: LDHKIM@korea.ac.kr
DOI:
https://doi.org/10.1530/JOE-21-0187
Volume/Issue:
Volume 251: Issue 3
Article Type:
Research Article
Page Range:
195–206
Online Publication Date:
08 Nov 2021
Copyright:
© Society for Endocrinology 2021
Restricted access
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Vascular reactivity of adipose tissue (AT) is hypothesized to play an important role in the development of obesity. However, the exact role of vascular reactivity in the development of obesity remains unclear. In this study, we investigated the chronological changes in vascular reactivity and the microenvironments of the visceral AT (VAT) and subcutaneous AT (SAT) in lean and obese mice. Changes in blood flow levels induced by a β-adrenoceptor agonist (isoproterenol) were significantly lower in the VAT of the mice fed a high-fat diet (HFD) for 1 and 12 weeks than those in the VAT of the mice fed a low-fat diet (LFD) for the same period; no significant change was observed in the SAT of any mouse group, suggesting depot-specific vascular reactivity of AT. Moreover, the hypoxic area and the expression of genes associated with angiogenesis and macrophage recruitment were increased in the VAT (but not in the SAT) of mice fed an HFD for 1 week compared with mice fed an LFD. These changes occurred with no morphological changes, including those related to adipocyte size, AT vessel density, and the diameter and pericyte coverage of the endothelium, suggesting a determinant role of vascular reactivity in the type of AT remodeling. The suppression of vascular reactivity was accompanied by increased endothelin1 (Edn1) gene expression and extracellular matrix (ECM) stiffness only in the VAT, implying enhanced contractile activities of the vasculature and ECM. The results suggest a depot-specific role of vascular reactivity in AT remodeling during the development of obesity.

Supplementary Materials

    • Figure S1. Schematic diagram of a micro-infusion method for evaluating adipose tissue vascular reactivity. Micro-infusion injectors (31-gauge needle) were inserted into epididymal visceral adipose tissue or inguinal subcutaneous adipose tissue, and saline or pharmacological agent infusion was started at a rate of 0.5 µl/min using a syringe pump. Changes in adipose tissue blood flow were detected using laser Doppler flowmetry.
    • Figure S2. Metabolic profiling of the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in mice fed either low-fat diet (LFD) or high-fat diet (HFD). (A) Body weight of mice fed LFD for 1 (n = 30) and 12 (n = 24) weeks or HFD for 1 (n = 28) and 12 (n = 27) weeks. (B) Total fat mass of mice fed LFD for 1 (n = 9) and 12 (n = 20) weeks or HFD for 1 (n = 10) and 12 (n = 17) weeks. (C, D) VAT mass and adipocyte number per VAT depot in mice fed either LFD or HFD for 1 week (n = 5 per group). (E, F) SAT mass and adipocyte number per SAT depot in mice fed either LFD or HFD for 1 week (n = 5 per group). *, P < 0.05, between LFD and HFD; #, P < 0.05 between 1 week and 12 weeks. Two-way ANOVA followed by Bonferroni's multiple comparison test (for A and B). Student’s t-test (for C-F).
    • Figure S3. Comparison of the response of adipose tissue blood flow (ATBF) to local ß-adrenergic stimulation and the expression levels of genes associated with angiogenesis and inflammation between the subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of mice fed a high-fat diet (HFD) for 12 weeks. (A) Comparison of the response of ATBF to local isoproterenol infusion (10-4 M) between the SAT (n = 11) and VAT (n = 16) of HFD-fed mice after 12 weeks. (B) Comparison of the expression levels of angiogenesis-associated genes between the SAT (n = 6) and VAT (n = 6) after 12 weeks of HFD exposure. (C, D) Comparison of the expression of genes related to macrophage recruitment and polarization (such as M1 and M2) in the SAT (n = 6) and VAT (n = 6) after 12 weeks of HFD exposure. *, P < 0.05; Student’s t-test.
    • Figure S4. Effect of aging on blood flow during continuous local infusion of isoproterenol (ISO) (10-6 M and 10-4 M) into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of mice fed either a low-fat diet (LFD) or high-fat diet (HFD). (A) Comparison of changes in blood flow after local ISO infusion into VAT of mice fed an LFD for 1 (n = 11) and 12 (n = 15) weeks. (B) Comparison of changes in blood flow after local ISO infusion into VAT of mice fed an HFD for 1 (n = 15) and 12 (n = 16) weeks. (C) Comparison of changes in blood flow after local ISO infusion into SAT of mice fed an LFD for 1 (n = 19) and 12 (n = 9) weeks. (D) Comparison of changes in blood flow after local ISO infusion into SAT of mice fed an HFD for 1 (n = 13) and 12 (n = 11) weeks. Fold change was represented relative to saline-infused adipose tissue blood flow (ATBF) (baseline). *, P < 0.05; Two-way ANOVA followed by Bonferroni's multiple comparison test.
    • Table S1. Mouse qPCR (TaqMan) Primer List
    • Table S2. Antibody List

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
12
Article Type:
Research Article
Received Date:
15 Sep 2021
Accepted Date:
05 Oct 2021
Print Publication Date:
01 Dec 2021
Online Publication Date:
08 Nov 2021
Keywords:
adipose tissue blood flow; beta-adrenergic receptor; hypoxia; adipose tissue remodeling; obesity

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