Renal transport of organic acids and bases in genetically obese mice.

Accumulation of p-aminohippurate (PAH) and N-methylnicotinamide (NMN) by renal cortical slices was used to estimate transport capacity for organic anions and cations, respectively. In a previous study, renal organic anion transport appeared to be selectively depressed in animals rendered obese by high fat feeding. However, the effects of obesity could not be discretely separated from the effects of the 30% fat diet used to produce the obesity. Genetically obese hyperglycemic mice provided a model to determine the effect of obesity on renal transport systems without the complication due to diet. Accumulation of both PAH and NMN was depressed in renal cortical slices from genetically obese mice. Addition of plasma from thin or obese animals increased PAH accumulation by slices from thin animals. Accumulation by slices from obese animals was unaffected by addition of plasma. Oxygen consumption with acetate in the medium was less in kidneys from obese mice than kidneys from thin mice. Thus, in addition to inhibition of transport capacity, renal cortex of genetically obese mice has a biochemical defect that prevents response to stimulators. It is concluded that several renal functions are depressed in the genetically obese hyperglycemic mouse. Whether the depressed function results from the obesity or is concomitant with the gene for obesity is as yet undertermined.