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

Yu-Jen Chen,Mei-Hui Wang,Tai-Yuan Chuang,Yi-Shan Chien,Yuan-Yu Lin,Chao-Wei Huang,Shinn-Chih Wu,Shih-Torng Ding,Wen-Hung Kuo,Harry J Mersmann,Pei-Xin Liao,Wen-Yuan Yang,Tzu-Hsuan Huang,Yu-Ju Peng,Chiao-Wei Lin

doi:10.3390/ijms22020906

Abstract

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 [18F] fluorodeoxyglucose-PET/CT (18F-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 Ucp1, 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 Ucp1, 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.

Highlights

Introduction conditions of the Creative CommonsThere are two distinct types of adipose tissues, brown (BAT) and white (WAT), in mammals including humans and mice
After a pre-test confirming temperature and time length described in Materials and a pre-test confirming temperature and time length described in Materials and Methods,After wild-type (WT) and transgenic porcine adiponectin receptor 1 (AdipoR1) mice were housed in a coldMethods, wild-type (WT) and transgenic porcine AdipoR1 mice were housed in a coldroomroom forfor two weeks
AdipoR1 female mice we focus on comparing WT female mice with AdipoR1 female mice

Summary

Introduction

There are two distinct types of adipose tissues, brown (BAT) and white (WAT), in mammals including humans and mice. Mice or rats constantly possess surgically obvious significant amounts of BAT, around the interscapular region, even in adulthood. Given BAT weights relative to total body weights, mouse BAT is quite large. It is believed that, unlike mice, human BAT only exists in infants and recedes in the growing period [2]. Until 2009, metabolically active BAT was clearly mapped within the supraclavicular region, correlated with cold stimulation and inversely correlated with body max index (BMI), obesity, or aging [3,4,5]. Recent interests about BAT development and methods to activate human and mouse BAT reignite adipose researchers

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