Collagen production in fasted and food-restricted rats: response to duration and severity of food deprivation.

Malnutrition is associated with defects in connective tissue metabolism such as altered growth and wound healing. Because collagen is the major protein in most tissues, we determined the threshold for induction of altered collagen production by partial food restriction in rats. Groups of animals were fasted 2 or 4 d or were fed 20-100% of a predetermined food intake for 4 to 8 d. Collagen and noncollagen protein production in articular cartilage were determined using purified collagenase digestion of collagen labeled for 2 h in vitro with [3H]proline. Significant decreases in collagen (P less than 0.01) were seen in rats after 4 d of 40% (weight-losing rats) or after 8 days of 80% (weight-gaining rats) ad libitum intake. Collagen production decreased with both duration and degree of food deprivation; after 8 d of 20% intake, collagen was less than 10% that of controls fed ad libitum (P less than 0.001). In contrast, noncollagen protein production was significantly decreased only after 4 or 8 d of less than 40% intake (weight-losing rats). Maximum suppression of noncollagen protein was to approximately 65% of levels in controls fed ad libitum (P less than 0.01) and was not further reduced in fasted rats. Insulin-like growth factor-I levels were significantly decreased with duration and severity of diet in parallel with changes in collagen. The degree and sensitivity of altered collagen production to small changes in food intake suggest close regulation of this peptide and a potential role for decreased collagen synthesis in connective tissues during mild states of undernutrition.