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Adipocyte enhancer-binding protein 1 modulates adiposity and energy homeostasis.

OBJECTIVE: To determine whether adipocyte enhancer binding protein (AEBP) 1, a transcriptional repressor that is down-regulated during adipogenesis, functions as a critical regulator of adipose tissue homeostasis through modulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) tumor suppressor activity and mitogen-activated protein kinase (MAPK) activation. RESEARCH METHODS AND PROCEDURES: We examined whether AEBP1 physically interacts with PTEN in 3T3-L1 cells by coimmunoprecipitation analysis. We generated AEBP1-null mice and examined the physiological role of AEBP1 as a key modulator of in vivo adiposity. Using adipose tissue from wild-type and AEBP1-null animals, we examined whether AEBP1 affects PTEN protein level. RESULTS: AEBP1 interacts with PTEN, and deficiency of AEBP1 increases adipose tissue PTEN mass. AEBP1-null mice have reduced adipose tissue mass and enhanced apoptosis with suppressed survival signal. Primary pre-adipocytes from AEBP1-null adipose tissues exhibit lower basal MAPK activity with defective proliferative potential. AEBP1-null mice are also resistant to diet-induced obesity, suggesting a regulatory role for AEBP1 in energy homeostasis. DISCUSSION: Our results suggest that AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes, as a key functional role in modulation of in vivo adiposity.

Pubmed ID: 17299101

Authors

  • Ro HS
  • Zhang L
  • Majdalawieh A
  • Kim SW
  • Wu X
  • Lyons PJ
  • Webber C
  • Ma H
  • Reidy SP
  • Boudreau A
  • Miller JR
  • Mitchell P
  • McLeod RS

Journal

Obesity (Silver Spring, Md.)

Publication Data

February 14, 2007

Associated Grants

None

Mesh Terms

  • 3T3-L1 Cells
  • Adipose Tissue, White
  • Adiposity
  • Animals
  • Apoptosis
  • Carboxypeptidases
  • Energy Metabolism
  • Female
  • Homeostasis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PTEN Phosphohydrolase
  • Protein Binding
  • Protein Processing, Post-Translational
  • Repressor Proteins