平井 静

We investigated the effect of activin A on differentiation of 3T3-L1 preadipocyte. Activin A suppressed the induction of terminal differentiation markers such as glycerol-3-phosphate dehydrogenase (GPDH) activity, lipid accumulation, and the expression of adipocyte fatty acid-binding protein (aP2) mRNA when the cells were treated with activin A throughout the differentiation period. Activin A treatment during the early phase decreased GPDH activity and aP2 mRNA level, and also reduced the expression of peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer binding protein (C/EBP) alpha mRNAs without affecting the expressions of the active isoforms of C/EBPbeta and its mRNA. On the other hand, activin A treatment had no effect on the mitotic clonal expansion. These results indicate that activin A inhibits adipogenesis via affecting the transcriptional factor cascade upstream of PPARgamma expression.

The effects of red yeast rice extracts (RE) on adipocyte differentiation of 3T3-L1 cells were studied. RE were extracted from embryonic rice fermented with red yeast (Monascus ruber). These extracts significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Moreover, mRNA expression levels of both CCAAT/enhancer-binding protein (C/EBP) alpha and peroxisome proliferator-activated receptor (PPAR) gamma, the key adipogenic transcription factors, were markedly decreased by RE. RE also inhibited the expression of PPARgamma at protein levels. RE decreased significantly gene expression of adipocyte fatty acid binding protein (aP2) and leptin, which are adipogenic marker proteins and C/EBPalpha and PPARgamma target genes. These results suggest that the inhibitory effect of RE on adipocyte differentiation might be mediated through the down-regulated expression of adipogenic transcription factors and other specific genes.

We investigated the effect of protein deficiency on mRNA levels of insulin-like growth factors (IGF-I and -II) and myostatin in skeletal muscle of weaned lambs. Weaned lambs were given a control diet (crude protein, 18%) or a low protein diet (crude protein, 5.7%) for 20 days. A small piece of the M. longissimus thoracis was collected by surgical biopsy at the end of feeding trial. The mRNAs of IGFs and myostatin were determined using a real-time reverse transcription polymerase chain reaction. Blood samples were also collected to measure plasma concentrations of IGF-I and serum urea nitrogen. Control lambs gained normally, whereas the bodyweight of the animals given the low protein diet was maintained and was significantly lower than that of the control from 10 days of the onset of feeding trial. Protein deficiency affected neither IGF mRNAs nor myostatin mRNA in the muscle. The expression of these mRNAs was unlikely to respond sensitively to protein deficiency in the muscle. However, serum IGF-I concentration was significantly lower in the protein deficient lambs than in the control animals. Therefore, we consider that the retardation of muscular growth does not depend on the local mRNA expression of these factors in protein deficient lambs, but the reduction of serum IGF-I, at least, partly contributes to the suppression of growth.