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Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice

  • Lee, Hye-Jin (Department of Pharmacology, Korea University College of Medicine) ;
  • Jin, Bo-Yeong (Department of Pharmacology, Korea University College of Medicine) ;
  • Park, Mi-Rae (Department of Pharmacology, Korea University College of Medicine) ;
  • Seo, Kwan Sik (Department of Rehabilitation Medicine, Seoul National University Hospital) ;
  • Jeong, Yong Taek (Department of Pharmacology, Korea University College of Medicine) ;
  • Choi, Sang-Hyun (Department of Pharmacology, Korea University College of Medicine) ;
  • Kim, Dong-Hoon (Department of Pharmacology, Korea University College of Medicine)
  • Received : 2021.01.23
  • Accepted : 2021.03.23
  • Published : 2021.07.01

Abstract

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (grant number 2017R1D1A1B03031216); the Ministry of Science & ICT (grant number 2015M3A9E7029172 & 2018R1A2B6001296); and a Korea University grant.

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