Discovery of melanin-concentrating hormone receptor 1 in brown adipose tissue

• Main Authors: Balber, T. (Author), Dumanic, M. (Author), Egger, G. (Author), Fürnsinn, C. (Author), Hacker, M. (Author), Herz, C.T (Author), Kiefer, F.W (Author), Klebermass, E.-M (Author), Kulterer, O.C (Author), Mitterhauser, M. (Author), Pallitsch, K. (Author), Philippe, C. (Author), Scherer, T. (Author), Scheuba, C. (Author), Spreitzer, H. (Author), Viernstein, H. (Author), Vraka, C. (Author), Wadsak, W. (Author), Zeilinger, M. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: 3 [[3 [4 (3 acetamidophenyl) 1 piperidinyl]propyl]carbamoyl] 4 (3,4 difluorophenyl) 1,2,3,4 tetrahydro 6 (methoxymethyl) 2 oxo 5 pyrimidinecarboxylic acid methyl ester; 5 [2 [[2 (3 chlorophenyl) 2 hydroxyethyl]amino]propyl] 1,3 benzodioxole 2,2 dicarboxylic acid; adipocyte; Adipose Tissue, Brown; adult; animal; animal experiment; animal model; animal tissue; Animals; Article; Bagg albino mouse; beta 3 adrenergic receptor; beta 3 adrenergic receptor stimulating agent; binding affinity; brown adipose tissue; C57BL mouse; cl316 243; controlled study; energy balance; fluorodeoxyglucose f 18; Fluorodeoxyglucose F18; gene expression; hormone receptor; human; human cell; human tissue; Humans; imaging; in vitro study; in vivo study; ligand binding; male; Male; MCHR1; melanin concentrating hormone receptor 1; melanin-concentrating hormone receptor; messenger RNA; metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; mouse; nonhuman; obesity; PET; positron emission tomography; Positron-Emission Tomography; protein function; protein protein interaction; rat; Rats; Rats, Sprague-Dawley; real time reverse transcription polymerase chain reaction; Receptors, Pituitary Hormone; Sprague Dawley rat; unclassified drug; Western blotting
• Online Access: View Fulltext in Publisher
• ISBN: 00778923 (ISSN)
• DOI: 10.1111/nyas.14563

Although extensive research on brown adipose tissue (BAT) has stimulated optimism in the battle against obesity and diabetes, BAT physiology and organ crosstalk are not fully understood. Besides BAT, melanin-concentrating hormone (MCH) and its receptor (MCHR1) play an important role in energy homeostasis. Because of the link between hypothalamic MCH neurons and sympathetic BAT activation via β-adrenoceptors, we investigated the expression and physiological role of the MCHR1 in BAT. MCHR1 was detected in rodent and human BAT with RT-qPCR and western blot analyses. In vivo imaging in rats used the glucose analog [18F]FDG and the MCHR1-tracer [11C]SNAP-7941. We found that the β3-adrenoceptor (ADRB3) agonist CL316,243 increased [11C]SNAP-7941 uptake in BAT. Additionally, a pharmacological concentration of SNAP-7941—a low-affinity ADRB3 ligand—stimulated [18F]FDG uptake, reflecting BAT activation. In cultured human adipocytes, CL316,243 induced MCHR1 expression, further supporting a direct interaction between MCHR1 and ADRB3. These findings characterized MCHR1 expression in rodent and human BAT for the first time, including in vitro and in vivo data demonstrating a link between MCHR1 and the β3-adrenergic system. The presence of MCHR1 in BAT emphasizes the role of BAT in energy homeostasis and may help uncover treatment approaches for obesity. © 2021 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences