Fat apoptosis through targeted activation of caspase 8: A new mouse model of inducible and reversible lipoatrophy

Utpal B. Pajvani, Maria E. Trujillo, Terry P. Combs, Puneeth Iyengar, Linda Jelicks, Kevin A. Roth, Richard N. Kitsis, Philipp E. Scherer

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

We describe the generation and characterization of the first inducible 'fatless' model system, the FAT-ATTAC mouse (fat apoptosis through targeted activation of caspase 8). This transgenic mouse develops identically to wild-type littermates. Apoptosis of adipocytes can be induced at any developmental stage by administration of a FK1012 analog leading to the dimerization of a membrane-bound, adipocyte-specific caspase 8-FKBP fusion protein. Within 2 weeks of dimerizer administration, FAT-ATTAC mice show near-knockout levels of circulating adipokines and markedly reduced levels of adipose tissue. FAT-ATTAC mice are glucose intolerant, have diminished basal and endotoxin-stimulated systemic inflammation, are less responsive to glucose-stimulated insulin secretion and show increased food intake independent of the effects of leptin. Most importantly, we show that functional adipocytes can be recovered upon cessation of treatment, allowing the study of adipogenesis in vivo, as well as a detailed examination of the importance of the adipocyte in the regulation of multiple physiological functions and pathological states.

Original languageEnglish (US)
Pages (from-to)797-803
Number of pages7
JournalNature Medicine
Volume11
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Caspase 8
Adipocytes
Chemical activation
Fats
Tacrolimus Binding Proteins
Apoptosis
Glucose
Adipokines
Dimerization
Leptin
Endotoxins
Fusion reactions
Insulin
Tissue
Membranes
Adipogenesis
Withholding Treatment
Transgenic Mice
Adipose Tissue
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pajvani, U. B., Trujillo, M. E., Combs, T. P., Iyengar, P., Jelicks, L., Roth, K. A., ... Scherer, P. E. (2005). Fat apoptosis through targeted activation of caspase 8: A new mouse model of inducible and reversible lipoatrophy. Nature Medicine, 11(7), 797-803. https://doi.org/10.1038/nm1262

Fat apoptosis through targeted activation of caspase 8 : A new mouse model of inducible and reversible lipoatrophy. / Pajvani, Utpal B.; Trujillo, Maria E.; Combs, Terry P.; Iyengar, Puneeth; Jelicks, Linda; Roth, Kevin A.; Kitsis, Richard N.; Scherer, Philipp E.

In: Nature Medicine, Vol. 11, No. 7, 07.2005, p. 797-803.

Research output: Contribution to journalArticle

Pajvani, UB, Trujillo, ME, Combs, TP, Iyengar, P, Jelicks, L, Roth, KA, Kitsis, RN & Scherer, PE 2005, 'Fat apoptosis through targeted activation of caspase 8: A new mouse model of inducible and reversible lipoatrophy', Nature Medicine, vol. 11, no. 7, pp. 797-803. https://doi.org/10.1038/nm1262
Pajvani, Utpal B. ; Trujillo, Maria E. ; Combs, Terry P. ; Iyengar, Puneeth ; Jelicks, Linda ; Roth, Kevin A. ; Kitsis, Richard N. ; Scherer, Philipp E. / Fat apoptosis through targeted activation of caspase 8 : A new mouse model of inducible and reversible lipoatrophy. In: Nature Medicine. 2005 ; Vol. 11, No. 7. pp. 797-803.
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