Site-specific control of rat preadipocyte adipose conversion by ovarian status: Possible involvement of CCAAT/enhancer-binding protein transcription factors.

The preadipocyte-adipocyte conversion process from two intraabdominal (parametrial and perirenal fat depots) is differently affected by ovarian status in the rat. We have tested the hypothesis that these site-specific alterations of adipogenesis might be related to changes in the expression of the transcription factors c-mycand CCAAT/enhancer binding proteins (C/EBPalpha, -beta, and -zeta) that regulate proliferation and differentiation. The increased proliferation rates observed in parametrial and perirenal preadipocytes after ovariectomy were not linked to variations in c-myc mRNA levels. Expression of the early marker of adipogenesis, lipoprotein lipase (LPL), remained insensitive to the ovarian status in early differentiated parametrial and perirenal preadipocytes. By contrast, LPL expression increased in early differentiated sc preadipocytes from ovariectomized rats, an effect that was completely reversed by in vivo estradiol and progesterone treatment. Expression of C/EBPbeta protein was unaffected by ovarian status whatever the anatomic origin of the preadipocytes. By contrast, the levels of p42 and p30 isoforms of C/EBPalpha were specifically decreased in parametrial preadipocytes, an alteration that was completely corrected by in vivo administration of estradiol and progesterone. C/EBPzeta, a dominant inhibitor of C/EBPalpha and -beta, exhibited a strong site-specific expression since C/ EBPzeta content was fivefold higher in sc preadipocytes than in deep intraabdominal cells whatever the ovarian status. Furthermore, ovariectomy selectively decreased C/EBPzeta levels in sc cells. In conclusion, our study suggests that some of the site-specific effects of ovariectomy on adipogenesis could involve, at least in part, altered expressions of C/EBPalpha and -zeta, both of which are important transcriptional regulators of fat cell differentiation and metabolism.