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.


METHODS
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.


CONCLUSIONS
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.
Ro
Hyo-Sung
HS
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada. hsro@dal.ca
Zhang
Lei
L
Majdalawieh
Amin
A
Kim
Sung-Woo
SW
Wu
Xue
X
Lyons
Peter J
PJ
Webber
Chris
C
Ma
Hong
H
Reidy
Shannon P
SP
Boudreau
Aaron
A
Miller
Jessica R
JR
Mitchell
Patricia
P
McLeod
Roger S
RS
D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000502:physiology; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D006706:Homeostasis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C112918:Aebp1 protein, mouse; D012097:Repressor Proteins; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D002268:Carboxypeptidases