title: Dietary fish oil reduces glomerular injury and elevated renal hydroxyeicosatetraenoic acid levels in the JCR:LA-cp rat, a model of the metabolic syndrome.
abstract: 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 PGF1α (PGI2 metabolite), thromboxane B2 (TxB2), PGF2α and PGD2 by approximately 60 % in rats fed 10 % fish oil, and TxB2 ( - 50 %) and PGF2α ( - 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.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. aukema@umanitoba.ca
authors.forename: Harold M
authors.initials: HM
authors.lastname: Aukema
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Faye
authors.initials: F
authors.lastname: Borthwick
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D019587:Dietary Supplements; D015237:Dinoprost / Q000378:metabolism; D004195:Disease Models, Animal; D005395:Fish Oils / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005838:Genotype; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005395:Fish Oils; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015230:Prostaglandin D2