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Role of angiotensin type 2 receptor in improving lipid metabolism and preventing adiposity

  • Sourashish Nag
  • Sanket Patel
  • Shailaja Mani
  • Tahir HussainEmail author
Article

Abstract

Recent studies on mice with null mutation of the angiotensin type 2 receptor (AT2R) gene have implicated the involvement of AT2R in regulating adipocyte size and obesity, a major risk factor for metabolic syndrome. However, the outcome from these studies remains inconclusive. Therefore, current study was designed to test whether pharmacological activation of AT2R regulates adiposity and lipid metabolism. Male mice (5-weeks old) were pre-treated with vehicle or AT2R agonist (C21, 0.3 mg/kg, i.p., daily, for 4 days) and fed normal diet (ND). Then these animals were subdivided into ND and high-fat diet (HFD) regimen and concomitantly treated with vehicle or C21 through day 14. Vehicle-treated HFD-fed mice demonstrated an increase in epididymal white adipose tissue (eWAT) weight and adipocyte size, which were associated with increased eWAT expression of the lipogenic regulators, fatty acid binding protein and fatty acid synthase, decreased expression of adipose triglyceride lipase and increased expression of hormone-sensitive lipase. Interestingly, C21 pre-treatment altered HFD-induced changes in lipogenic and lipolytic regulators. C21 pre-treatment prevented decrease in expression of uncoupler protein-1 in brown adipose in HFD-fed mice, which was associated with increased core temperature. In addition, C21 pre-treatment ameliorated plasma-free fatty acids, triglycerides, insulin and tumor necrosis factor-α in HFD-fed mice. Ex-vivo study in isolated primary epididymal adipocytes revealed that C21 inhibits long chain fatty acid transporter, via a nitric oxide synthase/guanylate cyclase/protein kinase G-dependent pathway. Collectively, we propose pharmacological activation of AT2R regulates fatty acid metabolism and thermogenesis and prevents HFD-induced adiposity in mice.

Keywords

Adipocyte AT2Fatty acid transporter (FATP) Lipid metabolism Adiposity 

Notes

Author contributions

SN and SP designed and performed the study and acquired, analyzed and interpreted data; SN, SP, SM and TH drafted the article and revised critically for important intellectual content; SN, SP, SM and TH approved the final version of the manuscript.

Funding

This work was supported by the National Institutes of Health grant R0I DK-61578 to TH and institutional funds.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11010_2019_3602_MOESM1_ESM.doc (184 kb)
Supplementary material 1 (DOC 183 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacological & Pharmaceutical Sciences, College of PharmacyUniversity of HoustonHoustonUSA
  2. 2.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  3. 3.Department of NeuroscienceBaylor College of MedicineHoustonUSA

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