Studies of the pathophysiological effects of fatty acid bearing albumin in models of proteinuric kidney disease

Proteinuria may be directly responsible for promoting tubulointerstitial injury. The fatty acids carried on filtered albumin are taken up by the proximal tubule, where they could contribute to tubulointerstitial injury.;The effects of fatty acid-albumin complexes have been studied in Opossum kidney (OK) cells, a proximal tubule cell line, OK cells transported two-thirds of 142C-palmitate-ablumin intracellularly within 16 hours. Less than 1% of 14C-palmitate taken up was isolated as intracellular free fatty acid. Less than 5% of 14 C-palmitate internalised was oxidised to 14CO2. 14C-palmitate-albumin was distributed into phosphatidylcholines, phosphatidylinositols, and triglycerides. 14C-labelled unsaturated fatty acid-albumins (oleate, linoleate and arachidonate) showed preferential incorporation into triglycerides, with lesser incorporation into phospholipids. Fatty acid-albumin uptake produced a marked 10-fold increase in total triglyceride levels. Oil Red O staining of OK cells cultured with oleate-albumin showed a marked increase in intracellular lipid droplets, indicating triglyceride accumulation. Different fatty acids, when taken up by the OK cell, have distinct metabolic fates. Each fatty acid is incorporated into certain specific complex lipids, possibly dependent on the presence or absence of double bonds.;The effects of fatty acid-albumin complexes on OK cell growth were studied. Palmitate-albumin and myristate-albumin markedly inhibited while oleate-albumin stimulated OK cell growth. The growth inhibitory effect of palmitate-albumin occurred in the absence of significant cellular toxicity, and was prevented by the presence of an equimolar concentration of oleate-albumin. Uptake of mainly saturated fatty acid-albumin complexes by the proximal tubule could inhibit its regeneration after injury.;The effects of fatty acid bearing albumin were studied in the protein-overload model of proteinuria.;In conclusion, this work has provided new evidence that the fatty acids carried out on albumin may have important metabolic and pathophysiological effects on the proximal tubule, which could contribute to the progression of proteinuric renal disease.