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
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
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions
- The Mechanism of White and Brown Adipocyte Differentiation
- Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders
- High-fat diet alters the thermogenic gene expression to β-agonists or 18-carbon fatty acids in adipocytes derived from the white and brown adipose tissue of mice
- Food Intake and Thermogenesis in Adipose Tissue
