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

Key Findings

Kidney disease can be an outcome of obesity related glomerulopathy (ORG). Here the hormone leptin which is associated with increased body fat and ORG was reduced by ALA.  A higher renal ALA to LA ratio was found. However, LA, renal LA, renal DHA as well as the content of dietary fat (25 per cent vs. 55 per cent energy) did not significantly impact renal pathology. The authors recommend an assessment if diets with a 1 to 2 ALA to LA ratio and 4.4 per cent of total calories as ALA to reduce glomerulomegaly, a marker for early ORG and ORG progression.

ABSTRACT

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 per cent 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 to  (g ALA to LA per 100 g oil) to  canola/flax (20 to 18), canola (8 to 18), soy (9 to 53), high oleic canola/canola (5 to 16), high-oleic canola (2 to 15), lard/soy (1 to 8), and safflower (0.2 to 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, proteinuria, change in proteinuria, and glomerular damage. Renal triglyceride ALA to LA was strongly correlated with dietary ALA to LA, and inversely associated with mean glomerular volume. 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. (Authors abstract)