Dietary fish oil reduces glomerular injury and elevated renal hydroxyeicosatetraenoic acid levels in the JCR:LA-cp rat, a model of the metabolic syndrome

We have previously shown nutritional intervention with fish oil (n-3 PUFA) to reduce numerous complications associated with the metabolic syndrome (MetS) in the JCR:LA-corpulent (cp) rat. In the present study, we sought to explore the potential role of fish oil to prevent glomerulosclerosis in JCR:LA-cp rats via renal eicosanoid metabolism and lipidomic analysis. Male lean and MetS JCR:LA-cp rats were fed a lipid-balanced diet supplemented with fish oil (5 or 10% of total fat). After 16 weeks of feeding, albuminuria was significantly reduced in MetS rats supplemented with 5 or 10% fish oil (-53 and -70 %, respectively, compared with the untreated MetS rats). The 5% fish oil diet resulted in markedly lower glomerulosclerosis (-43 %) in MetS rats and to a lesser extent in those supplemented with 10% fish oil. Interestingly, untreated MetS rats had higher levels of 11- and 12-hydroxyeicosatetraenoic acids (HETE) v. lean rats. Dietary fish oil reduced these levels, as well as other (5-, 9- and 15-) HETE. Whilst genotype did not alter prostanoid levels, fish oil reduced endogenous renal levels of 6-keto PGF(1 alpha) (PGI(2) metabolite), thromboxane B-2 (TxB(2)), PGF(2 alpha) and PGD(2) by approximately 60% in rats fed 10% fish oil, and TxB(2) (-50 %) and PGF(2 alpha) (-41 %) in rats fed 5% fish oil. In conclusion, dietary fish oil prevented glomerular damage in MetS rats and mitigated the elevation in renal HETE levels. These results suggest a potential role for dietary fish oil to improve dysfunctional renal eicosanoid metabolism associated with kidney damage during conditions of the MetS.