Rat hepatic mRNA-S14 and lipogenic enzymes during weaning: role of S14 in lipogenesis.

The rapid and marked response of hepatic mRNA-S14 sequence to both triiodothyronine and carbohydrate intake has made this sequence an attractive model for studying the action of hormonal and dietary factors. Because it is highly expressed and regulated only in lipogenic tissues, we have suggested that it plays a role in some aspect of lipid synthesis, transport, or metabolism. To provide more precise information regarding the function of S14 we have measured lipogenesis, lipogenic enzymes, beta-oxidation, and mRNA-S14 levels in spontaneously weaning neonatal rats and in rats prematurely weaned to a laboratory diet on postnatal day 17. After birth, the levels of lipogenesis, mRNA-S14, and the lipogenic enzymes malic enzyme (ME) and fatty acid synthase (FAS) were almost undetectable but increased with the onset of spontaneous weaning. Coincident with these changes, beta-oxidation decreased. Premature weaning beginning on day 17 resulted in an earlier and even more marked increase in lipogenesis, ME, FAS, and mRNA-S14. On day 19, ME and FAS activities were 6- to 19-fold more than activities in control suckling pups, whereas mRNA-S14 levels had risen to greater than 100 times the control values. Thus directional shifts in mRNA-S14 corresponded with indices of lipogenesis and were opposite to indices reflecting beta-oxidation. The response of mRNA-S14 therefore suggests that it may be related to the synthesis of fatty acids. On the other hand, the level of lipogenesis in the fetus was high despite the fact that the levels of both mRNA-S14 and ME were low. This dissociation raises the possibility that the S14 protein participates in lipogenesis in the neonate and adult but not in the fetus.