title: Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice.
abstract: Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA1c, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects.
authors.affiliation: Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Hesselbarth
authors.affiliation: Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pettinelli
authors.affiliation: Institute of Anatomy, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.affiliation: IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Berger
authors.affiliation: German Center for Diabetes Research (DZD), Leipzig, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kunath
authors.affiliation: Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig, Germany. Electronic address: nora.kloeting@medizin.uni-leipzig.de.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1
chemical_list: D005230:Fatty Acids, Nonesterified; D005947:Glucose; D006442:Glycated Hemoglobin; D007473:Ion Channels; D019394:Ki-67 Antigen; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D014280:Triglycerides; D000071256:Uncoupling Protein 1; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; C517652:hemoglobin A1c protein, human
keywords: Adipose tissue; Body composition; Browning; C57BL/6; Tamoxifen; UCP-1