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Clemmensen, C. ; Jall, S. ; Kleinert, M. ; Quarta, C. ; Gruber, T. ; Reber, J. ; Sachs, S. ; Fischer, K. ; Feuchtinger, A. ; Karlas, A. ; Simonds, S.E.* ; Grandl, G. ; Loher, D. ; Sanchez-Quant, E. ; Keipert, S. ; Jastroch, M. ; Hofmann, S.M. ; Nascimento, E.B.M.* ; Schrauwen, P.* ; Ntziachristos, V. ; Cowley, M.A.* ; Finan, B. ; Müller, T.D. ; Tschöp, M.H.

Coordinated targeting of cold and nicotinic receptors synergistically improves obesity and type 2 diabetes.

Nat. Commun. 9:4304 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Pharmacological stimulation of brown adipose tissue (BAT) thermogenesis to increase energy expenditure is progressively being pursued as a viable anti-obesity strategy. Here, we report that pharmacological activation of the cold receptor transient receptor potential cation channel subfamily M member 8 (TRPM8) with agonist icilin mimics the metabolic benefits of cold exposure. In diet-induced obese (DIO) mice, treatment with icilin enhances energy expenditure, and decreases body weight, without affecting food intake. To further potentiate the thermogenic action profile of icilin and add complementary anorexigenic mechanisms, we set out to identify pharmacological partners next to icilin. To that end, we specifically targeted nicotinic acetylcholine receptor (nAChR) subtype alpha3beta4 (α3β4), which we had recognized as a potential regulator of energy homeostasis and glucose metabolism. Combinatorial targeting of TRPM8 and nAChR α3β4 by icilin and dimethylphenylpiperazinium (DMPP) orchestrates synergistic anorexic and thermogenic pathways to reverse diet-induced obesity, dyslipidemia, and glucose intolerance in DIO mice.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brown Adipose-tissue; Optimal Housing Temperatures; Central-nervous-system; Thermal Environment; Energy-expenditure; Acetylcholine-receptors; Optoacoustic Tomography; Body-temperature; Healthy-adults; Trp Channels
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 4304 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Biological and Medical Imaging (IBMI)
Research Unit Analytical Pathology (AAP)
Institute of Diabetes and Regeneration Research (IDR)