Activating transcription factor 4 regulates adipocyte differentiation via altering the coordinate expression of CCATT/enhancer binding protein β and peroxisome proliferator-activated receptor γ.

Adipose tissue is crucial for energy homeostasis and is a topic interest with respect to investigating the regulation of adipose tissue formation for the ever-increasing health concerns of obesity and type 2 diabetes. Adipocyte differentiation is tightly regulated by the characteristic sequential expression change of adipocyte genes, including members of the CCATT/enhancer binding protein (C/EBP) family of transcription factors, peroxisome proliferator-activated receptor γ and tribbles homolog 3. In the present study, we demonstrate that C/EBPβ and peroxisome proliferator-activated receptor γ (but not tribbles homolog 3) are targeted for activation by activating transcription factor 4 (ATF4), a member of cAMP response element-binding/activator transcription factor family. Importantly, overexpression of ATF4 in 3T3-L1 cells enhanced adipogenesis, whereas small-interfering ATF4 blocked conversion of preadipocytes to adipocytes. These findings were accomplished by altering the coordinate expression of adipogenic transcription factors. Taken together, our results suggest that ATF4 is a positive regulator of adipocyte differentiation. This notion is also supported by the results of the present study showing that the expression of ATF4 is induced during adipocyte differentiation. Thus, ATF4 could be an important regulator of energy homeostasis.