Adipocyte Enhancer‐Binding Protein 1 Modulates Adiposity and Energy Homeostasis

Abstract

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.