Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to gen...

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Main Authors: Yu-Jen Chen, Chiao-Wei Lin, Yu-Ju Peng, Chao-Wei Huang, Yi-Shan Chien, Tzu-Hsuan Huang, Pei-Xin Liao, Wen-Yuan Yang, Mei-Hui Wang, Harry J. Mersmann, Shinn-Chih Wu, Tai-Yuan Chuang, Yuan-Yu Lin, Wen-Hung Kuo, Shih-Torng Ding
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/2/906
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author Yu-Jen Chen
Chiao-Wei Lin
Yu-Ju Peng
Chao-Wei Huang
Yi-Shan Chien
Tzu-Hsuan Huang
Pei-Xin Liao
Wen-Yuan Yang
Mei-Hui Wang
Harry J. Mersmann
Shinn-Chih Wu
Tai-Yuan Chuang
Yuan-Yu Lin
Wen-Hung Kuo
Shih-Torng Ding
author_facet Yu-Jen Chen
Chiao-Wei Lin
Yu-Ju Peng
Chao-Wei Huang
Yi-Shan Chien
Tzu-Hsuan Huang
Pei-Xin Liao
Wen-Yuan Yang
Mei-Hui Wang
Harry J. Mersmann
Shinn-Chih Wu
Tai-Yuan Chuang
Yuan-Yu Lin
Wen-Hung Kuo
Shih-Torng Ding
author_sort Yu-Jen Chen
collection DOAJ
description Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [<sup>18</sup>F] fluorodeoxyglucose-PET/CT (<sup>18</sup>F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic <i>Ucp1</i>, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic <i>Ucp1</i>, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.
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spelling doaj.art-540e103f423a4ebba9596682c56e9bf12023-12-03T13:39:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122290610.3390/ijms22020906Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in MiceYu-Jen Chen0Chiao-Wei Lin1Yu-Ju Peng2Chao-Wei Huang3Yi-Shan Chien4Tzu-Hsuan Huang5Pei-Xin Liao6Wen-Yuan Yang7Mei-Hui Wang8Harry J. Mersmann9Shinn-Chih Wu10Tai-Yuan Chuang11Yuan-Yu Lin12Wen-Hung Kuo13Shih-Torng Ding14Institute of Biotechnology, National Taiwan University, Taipei 10617, TaiwanInstitute of Biotechnology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanInstitute of Nuclear Energy Research, Taoyuan 325, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanInstitute of Biotechnology, National Taiwan University, Taipei 10617, TaiwanDepartment of Athletics, National Taiwan University, Taipei 10617, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10617, TaiwanInstitute of Biotechnology, National Taiwan University, Taipei 10617, TaiwanAdult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [<sup>18</sup>F] fluorodeoxyglucose-PET/CT (<sup>18</sup>F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic <i>Ucp1</i>, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic <i>Ucp1</i>, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.https://www.mdpi.com/1422-0067/22/2/906adiponectinadiponectin receptor 1beige adipose tissuebrown adipose tissuecold-induced thermogenesisPET/CT scintigraphy
spellingShingle Yu-Jen Chen
Chiao-Wei Lin
Yu-Ju Peng
Chao-Wei Huang
Yi-Shan Chien
Tzu-Hsuan Huang
Pei-Xin Liao
Wen-Yuan Yang
Mei-Hui Wang
Harry J. Mersmann
Shinn-Chih Wu
Tai-Yuan Chuang
Yuan-Yu Lin
Wen-Hung Kuo
Shih-Torng Ding
Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
International Journal of Molecular Sciences
adiponectin
adiponectin receptor 1
beige adipose tissue
brown adipose tissue
cold-induced thermogenesis
PET/CT scintigraphy
title Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
title_full Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
title_fullStr Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
title_full_unstemmed Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
title_short Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
title_sort overexpression of adiponectin receptor 1 inhibits brown and beige adipose tissue activity in mice
topic adiponectin
adiponectin receptor 1
beige adipose tissue
brown adipose tissue
cold-induced thermogenesis
PET/CT scintigraphy
url https://www.mdpi.com/1422-0067/22/2/906
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