Factors Contributing to Depressed Renal Transport of Organic Anions in the Obese Rat 1

Abstract

Summary

The effect of obesity produced by feeding rats a 60% fat diet (HF) on accumulation of the organic anion p-amino-hippurate (PAH) by renal cortical slices was determined using an in vitro technique. The rate of PAH uptake was determined and analyzed kinetically using a Lineweaver-Burk plot. In control rats fed a grain ration (GR) the V _max and K_m were less in old (60 wk) than in young (12 wk) animals. The animals on high fat (HF) had V _max and K_m values less than the respective age controls. The decrease in apparent affinity and maximal velocity with age and diet could indicate noncompetitive inhibition. The differences observed in PAH transport in the HF animals were not the result of differences in oxygen consumption, histology (light microscopy) or composition of renal cortical slices. Kidneys from animals fed HF and switched to GR at least 2 days prior to sacrificing accumulated PAH as well as those from animals fed GR from weaning. Kidneys from animals fed GR and switched to HF for at least 2 days had depressed PAH accumulation. Organic cation transport as determined with N-methylnicotinamide (NMN) accumulation was unaffected by diet switching. These data indicate the presence of some factor inhibiting PAH accumulation, perhaps of dietary origin (as another organic acid), in the serum. However, stimulation, not inhibition, was demonstrated when serum from the HF or control animals was added to the incubation medium. The data are consistent with the hypothesis that in the HF animals there is some factor which is probably tightly bound in the kidney but is present in such low concentrations in the serum that no acute inhibitory effects on PAH accumulation are demonstrable in vitro.