Dietary flax oil rich in α-linolenic acid reduces renal disease and oxylipin abnormalities, including formation of docosahexaenoic acid derived oxylipins in the CD1-pcy/pcy mouse model of nephronophthisis .

Key Findings:

The CD1-pcy per pcy (pcy) mouse is a model used to simulate nephronophthisis (NPHP), an inherited juvenile type of cystic kidney disease. Oxylipins are produced from fatty acids upon their release from tissue phospholipids by phospholipase A2 and conversion by cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) enzymes. Oxylipids have different physiological functions and can be altered in disease. Previous research has shown that flaxseed oil in the pcy mouse can reduce symptoms of the disease. In this study, flax oil feeding did not alter renal phospholipid DHA but did increase DHA oxylipins to levels similar to normal. ALA conversion to DHA appears to be occurring at a rate sufficient to restore DHA oxylipin levels and suggests that the regulation of ALA conversion to DHA may depend on the need for oxylipin production.  The flaxseed oil diet did reduce renal disease progression and provides evidence for physiologically meaningful conversion of ALA to DHA.

ABSTRACT:

The CD1 minus pcy/pcy mouse model of nephronophthisis displays reduced renal docosahexaenoic acid (DHA) levels and alterations in renal cycloxygenase and lipoxygenase oxylipins derived from n minus 6 fatty acids. Since dietary flax oil ameliorates disease progression, its effect on renal fatty acids and oxylipins was examined.  Sixteen weeks of feeding resulted in reduced disease progression and enrichment of renal phospholipid a-linolenic acid (ALA) and eicosapentaenoic acid, reduction in arachidonic acid (AA), but no change in linoleic acid (LA) or DHA.  In diseased kidneys, flax oil feeding mitigated the elevated levels of renal cyclooxygenase derived oxylipins formed from AA and the lowered lipoxygenase and cytochrome P450 derived oxylipins formed from ALA and DHA.  Increased DHA oxylipins occurred with flax feeding despite not altering DHA levels.  Dietary flax oil may therefore reduce disease progression via mitigation of oxylipin abnormalities.  This study also provides evidence in vivo ALA conversion to DHA in amounts necessary to restore DHA oxylipin levels. (Author’s abstract)