Different mechanisms decrease hepatic collagen and albumin production in fasted rats.

Weight loss is correlated with a specific decrease in collagen synthesis in extrahepatic tissues, mainly through modulation of mRNA levels. Here, we investigated the response to weight loss in the rat liver. Male rats were either fed ad libitum or fasted for 92 hr; fasted animals lost approximately 20% of their initial body weight. Following i.p. injection of [5-3H]proline, hepatic collagen was extracted and de novo collagen production was measured. There was a decrease in the specific radioactivities of purified hepatic collagen (-75%) and albumin (-70%) relative to total hepatic protein, indicating that production of both of these proteins was specifically decreased. In fasted animals, the absolute hepatic collagen production was markedly decreased (-60%), while changes in absolute hepatic protein production were small (-15%). Using hybridization with specific DNA probes, we found that fasting causes about a 70% decrease in albumin mRNA, but the quantities of hepatic procollagen alpha 1(I) and alpha 2(I) mRNAs were unchanged. These results are consistent with regulation of albumin production during fasting by modulation of mRNA levels. The inhibition of hepatic collagen production in fasted animals, however, appears to be modulated at a posttranscriptional level or may result from increased degradation. This response differs from the pretranslational regulation of collagen synthesis in extrahepatic tissues during fasting. Furthermore, our results suggest that decreased body weight could be a potentially complicating variable in studies of collagen metabolism and fibrogenesis in the liver.