title: Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy.
abstract: Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B₂. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6; Department of Physiology, University of Manitoba, Winnipeg, Canada R3E 0J9.
authors.forename: Stephanie P B
authors.initials: SP
authors.lastname: Caligiuri
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Declercq
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6; Department of Physiology, University of Manitoba, Winnipeg, Canada R3E 0J9; Manitoba Institute of Child Health, Winnipeg, Canada R3E 3P4.
authors.forename: Carla G
authors.initials: CG
authors.lastname: Taylor
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6; Department of Physiology, University of Manitoba, Winnipeg, Canada R3E 0J9.
authors.forename: Peter
authors.initials: P
authors.lastname: Zahradka
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Manitoba Institute of Child Health, Winnipeg, Canada R3E 3P4.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Ogborn
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 2N2; Canadian Centre for Agri-Food Research in Medicine, St Boniface Hospital Research Centre, Winnipeg, Canada R2H 2A6; Manitoba Institute of Child Health, Winnipeg, Canada R3E 3P4. Electronic address: harold.aukema@umanitoba.ca.
authors.forename: Harold M
authors.initials: HM
authors.lastname: Aukema
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000375:Aging; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects*; D018450:Disease Progression; D005355:Fibrosis; D006984:Hypertrophy; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D044243:Linoleic Acids, Conjugated / Q000009:adverse effects*; D008262:Macrophage Activation; D008565:Membrane Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000276:immunology / Q000503:physiopathology*; D054883:Oxylipins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011924:Rats, Zucker; D051437:Renal Insufficiency / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013929:Thromboxane B2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D044243:Linoleic Acids, Conjugated; D008565:Membrane Proteins; D054883:Oxylipins; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat
keywords: COX; Conjugated linoleic acid isomers; Kidney pathology; Obesity; Oxylipins