Compensatory increase in intestinal apolipoprotein A-IV mRNA levels in the experimental nephrotic rat

Using experimental nephrotic rats, we investigated the potential feedback regulation of apolipoproteins (apos) at their hepatic and intestinal synthetic sites. Nephrotic syndrome (NS) was induced in rats by puromycin aminonucleoside (PAN) with a single intraperitoneal injection (120 mg/kg). In nephrotic rats, we observed a 60% reduction in serum apo A-IV levels despite a 3.4-fold increase in jejunum and a 1.5-fold increase in ileum apo A-IV mRNA levels, although hepatic apo A-IV levels were unchanged compared with those in pair-fed control rats. A strikingly positive correlation was observed between daily urinary excretion of apo A-IV and its mRNA levels in jejunum (r = .856, P < .01; n = 10) and ileum (r = .710, P < .05; n = 10). On the other hand, nephrotic rats had an 8.2-fold increase in serum apo A-I level associated with a 4.6-fold increase in hepatic and a small but significant increase in jejunum apo A-I mRNA levels. Compared with the fractional catabolic loss of albumin or apo A-IV, that of apo A-I was small and suggests a diminished level of glomerular filtration, leading to a further elevation in serum apo A-I level. Barring nonspecific effects of PAN, these data suggest that reduction of serum apo A-IV level due to urinary loss may directly upregulate mRNA levels in the small intestine. Alternatively, it may be the result of an effective filtration of a serum component unassociated with lipoproteins that normally and site-specifically reduces apo A-I and apo A-IV mRNA transcription.