Original Article

Obesity (2007) 15, 288–302; doi:10.1038/oby.2007.569

Adipocyte Enhancer-Binding Protein 1 Modulates Adiposity and Energy Homeostasis*

Hyo-Sung Ro1, Lei Zhang1, Amin Majdalawieh1, Sung-Woo Kim*, Xue Wu1, Peter J. Lyons1, Chris Webber1, Hong Ma1, Shannon P. Reidy1, Aaron Boudreau†, Jessica R. Miller1, Patricia Mitchell1 and Roger S. McLeod1

  1. *Department of Immunology, The Scripps Research Institute, La Jolla, California.
  2. †Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California.
  3. 1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Correspondence: Hyo-Sung Ro Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Tupper Medical Building, 1850 College Street, Halifax, Nova Scotia, Canada B3H 1X5. E-mail: hsro@dal.ca

*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8 May 2006; Revised  00; Accepted 7 September 2006.

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Abstract

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.

Keywords:

adipose tissue, energy balance, mouse models, phosphatase and tensin homolog deleted on chromosome ten, mitogen-activated protein kinase

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