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Life without white fat: a transgenic mouse
1Laboratory of Biochemistry, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892 USA.
Genes & Development
|October 24, 1998
Summary
Researchers created a transgenic mouse lacking white adipose tissue by inhibiting key transcription factors. This mouse model exhibits severe metabolic dysfunction, including diabetes, and offers insights into lipoatrophic diabetes.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Diseases
Background:
- Adipose tissue plays a crucial role in energy homeostasis and metabolic regulation.
- Understanding the genetic regulation of adipogenesis is vital for metabolic disease research.
- The C/EBP and Jun families of transcription factors are critical for adipocyte development.
Purpose of the Study:
- To generate and characterize a mouse model lacking white adipose tissue.
- To investigate the physiological and metabolic consequences of complete adiposity loss.
- To establish a model for studying lipoatrophic diabetes and related metabolic disorders.
Main Methods:
- Generation of transgenic mice (A-ZIP/F-1) expressing a dominant-negative A-ZIP/F protein.
- The A-ZIP/F protein inhibits DNA binding of C/EBP and Jun transcription factors.
- Phenotypic analysis, including metabolic profiling and physiological assessments.
Main Results:
- Transgenic mice completely lack white adipose tissue and have reduced brown adipose tissue.
- Mice exhibit severe metabolic disturbances: diabetes, hyperinsulinemia, dyslipidemia, and hepatic steatosis.
- Phenotype includes growth delay, reduced fecundity, premature death, and sensitivity to anesthesia.
Conclusions:
- The absence of white adipose tissue leads to profound physiological and metabolic derangements.
- The A-ZIP/F-1 mouse serves as a valuable model for lipoatrophic diabetes (Seip-Berardinelli syndrome).
- This model elucidates the critical role of adipose tissue in overall metabolic health.