Exp Mol Med.  2003 Dec;35(6):518-526.

Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells

Affiliations
  • 1The Department of Life Science and the Research Institute for Natural Sciences, College of Natural Sciences Hanyang University, Seoul 133-791, Korea.
  • 2Department of Biotechnology, Konkuk University, Chungju 380-701, Korea. cgkim@hanyang.ac.kr
  • 3Samsung Biomedical Research Institute, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
  • 4Department of Internal Medicine, College of Medicine Hanyang University, Seoul 133-791, Korea.

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.

Keyword

adipocyte differentiation; brown adipose tissue; energy homeostasis; genetic tissue ablation; transgenic mice

MeSH Terms

Adipose Tissue/*cytology/drug effects/metabolism/ultrastructure
Aging/physiology
Animals
Body Weight
Carrier Proteins/genetics/metabolism
*Cell Differentiation/drug effects
Ganciclovir/pharmacology
Ion Channels
Leptin/metabolism
Membrane Proteins/genetics/metabolism
Mice
Mice, Transgenic
Mitochondrial Proteins
Obesity/chemically induced
Organ Specificity
Thymidine Kinase/genetics/metabolism
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