Evidence for the use of glomerulomegaly as a surrogate marker of glomerular damage and for alpha-linolenic acid-rich oils in the treatment of early obesity-related glomerulopathy in a diet-induced rodent model of obesity

Obesity-related glomerulopathy (ORG) is a unique and emerging condition that can lead to renal failure. Early detection, aided by an earlier diagnostic marker, would improve patient outcomes; this could be facilitated by an accurate model. Such a model would be useful to examine interventions like d...

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Published in:Applied physiology, nutrition, and metabolism nutrition, and metabolism, 2014-08, Vol.39 (8), p.951-959
Main Authors: Caligiuri, Stephanie P B, Blydt-Hansen, Tom, Love, Karin, Grégoire, Mélanie, Taylor, Carla G, Zahradka, Peter, Aukema, Harold M
Format: Article
Language:English
Subjects:
acides gras n-3
alpha-Linolenic Acid - therapeutic use
Animals
Biomarkers
Diet
Dietary Fats, Unsaturated - therapeutic use
Disease Models, Animal
Fatty acids
Health aspects
Hypertrophy - diet therapy
Hypertrophy - etiology
Kidney diseases
Kidney Diseases - diet therapy
Kidney Diseases - etiology
Kidney Glomerulus - pathology
maladie rénale
Male
Medical research
Medicine, Experimental
n-3 fatty acids
Obesity
Obesity - complications
obésité
Rats
Rats, Sprague-Dawley
renal disease
Studies
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Summary:Obesity-related glomerulopathy (ORG) is a unique and emerging condition that can lead to renal failure. Early detection, aided by an earlier diagnostic marker, would improve patient outcomes; this could be facilitated by an accurate model. Such a model would be useful to examine interventions like dietary fatty acids, which are known to influence renal diseases in later stages. In this study, obese-prone rats were provided high-fat (55% of energy) diets for 12 weeks to generate a model of diet-induced obesity. The rats were subsequently provided dietary oils with various levels of alpha-linolenic acid (ALA) and linoleic acid (LA) for 8 weeks, as follows: (g ALA:LA per 100 g oil): canola/flax (20:18), canola (8:18), soy (9:53), high-oleic canola/canola (5:16), high-oleic canola (2:15), lard/soy (1:8), and safflower (0.2:73). The model developed obesity, glomerulomegaly, proteinuria, and scarce glomerular damage with an indolent course. Morphometry and histology revealed glomerulomegaly as the first renal structural alteration. The utility of this marker as a predictor for the presence of ORG and renal injury was evidenced by its correlation to visceral adiposity (p < 0.0001, r = 0.44), proteinuria (p < 0.0001, ρ = 0.55), change in proteinuria (p = 0.0092, ρ = 0.42), and glomerular damage (p < 0.0001, ρ = 0.48). Renal triglyceride ALA:LA was strongly correlated with dietary ALA:LA (p < 0.0005, ρ = 0.96), and inversely associated with mean glomerular volume (p = 0.02, ρ = –0.82). The diet-induced obese model accurately represents early ORG, and implicates glomerulomegaly as an early surrogate diagnostic marker. Early intervention with ALA-rich dietary oils slowed glomerular enlargement; these findings warrant further clinical investigation to promote optimal patient outcomes.
ISSN:1715-5312
1715-5320
DOI:10.1139/apnm-2013-0476