title: Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells.
abstract: Adipose tissue is an important endocrine regulator of glucose metabolism and energy homeostasis. Researches have focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Brown adipose tissue (BAT) additionally plays a unique role in thermoregulation through the mitochondrial uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation. As a genetic tissue ablation model of BAT, we made transgenic mice expressing herpes simplex virus thymidine kinase (HSV-TK) driven by the brown adipocyte- specific UCP1 minimal regulatory element. The HSV-TK transgene was expressed specifically in BAT and more than 35% increase of apoptosis was induced by ganciclovir (GCV) treatment. Nevertheless, the expression level was not high enough to induce BAT ablation in GCV-treated adult mice. Importantly, however, we found that brown adipocytes in the periphery of interscapular BAT were transformed into white adipocyte-like unilocular cells. These cells express white adipocyte-specific leptin protein but are different in the ultrastructure of mitochondria from classical white adipocytes. Our data indicates that atrophy of BAT causes transformation into white adipocyte-like cells in the adult mouse and also suggests that further molecular understanding of adipocyte plasticity using our transgenic mouse model might be beneficial for the development of anti-obesity/anti-diabetic therapies.
authors.affiliation: The Department of Life Science and the Research Institute for Natural Sciences, College of Natural Sciences Hanyang University, Seoul 133-791, Korea.
authors.forename: Dae Whan
authors.initials: DW
authors.lastname: Kim
authors.forename: Beom Sue
authors.initials: BS
authors.lastname: Kim
authors.forename: Hee-Seok
authors.initials: HS
authors.lastname: Kwon
authors.forename: Chan Gil
authors.initials: CG
authors.lastname: Kim
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
authors.forename: Woong Hwan
authors.initials: WH
authors.lastname: Choi
authors.forename: Chul Geun
authors.initials: CG
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins; D009765:Obesity / Q000139:chemically induced; D009928:Organ Specificity; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D013937:Thymidine Kinase; D015774:Ganciclovir