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Published on: October 13, 2018
Late onset of obesity in male androgen receptor-deficient (AR KO) mice
Takashi Sato1, Takahiro Matsumoto, Takashi Yamada
1Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Japan.
Abstract:
An androgen receptor (AR) null mutant mice line was generated by means of a Cre-lox P system. The male (AR(L-/Y)) (KO) mice exhibited typical features of testicular feminization mutant (Tfm) disease in external reproductive organs with growth retardation. The growth curve of the male AR KO mice was similar to that of the wild-type female littermates until the 10th week of age, but thereafter a drastic increase in the growth was observed with development of obesity. Clear increase in the wet weights of white adipose tissues, but not of brown adipose tissue, was found in the 30-week-old male AR KO mice. However, no significant alteration in serum lipid parameters and food intake was observed. Thus, the present results suggest that AR may serve as a negative regulator of adipose development in adult males.
Insights
Androgen receptor (AR) null mutant mice developed obesity and increased white adipose tissue, suggesting AR negatively regulates fat development in adult males. This finding is crucial for understanding metabolic disorders.
Area of Science:
- Endocrinology
- Molecular Biology
- Metabolic Research
Background:
- The androgen receptor (AR) plays a critical role in male sexual development and function.
- Dysregulation of AR signaling is implicated in various diseases, including metabolic disorders.
- Understanding AR's role in adult physiology beyond reproduction is essential.
Purpose of the Study:
- To investigate the physiological consequences of complete androgen receptor deficiency in adult male mice.
- To determine the impact of AR null mutation on growth, body composition, and metabolic parameters.
- To elucidate the potential role of AR as a regulator of adipose tissue development.
Main Methods:
- Generation of an androgen receptor (AR) null mutant mouse line using the Cre-lox P system.
- Phenotypic characterization of male AR knockout (AR(L-/Y)) mice, including growth assessment and body composition analysis.
- Measurement of white and brown adipose tissue weights, serum lipid profiles, and food intake.
Main Results:
- Male AR KO mice exhibited features of testicular feminization and growth retardation, similar to wild-type females until 10 weeks of age.
- A significant increase in growth and development of obesity was observed in male AR KO mice after 10 weeks.
- Increased wet weights of white adipose tissue, but not brown adipose tissue, were noted in 30-week-old male AR KO mice, without changes in serum lipids or food intake.
Conclusions:
- The androgen receptor (AR) appears to function as a negative regulator of adipose tissue development in adult male mammals.
- AR deficiency leads to obesity and altered body composition, highlighting its importance in metabolic homeostasis.
- These findings provide new insights into the role of AR in regulating energy balance and preventing obesity in adult males.
