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Life without white fat: a transgenic mouse

J Moitra1, M M Mason, M Olive

  • 1Laboratory of Biochemistry, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892 USA.

Genes & Development
|October 24, 1998
PubMed
Summary
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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.

Related Experiment Videos

  • 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.