Dietary Linoleic Acid and a-Linolenic Acid Differentially Affect Renal Oxylipins and Phospholipid Fatty Acids in Diet induced Obese Rats
Dietary Linoleic Acid and a-Linolenic Acid Differentially Affect Renal Oxylipins and Phospholipid Fatty Acids in Diet induced Obese Rats
Year: 2013
Authors: Caligiuri, S.P.B. Love, K. Winter, T. Gauthier, J. Taylor, C.G. Blydt-Hansen, T. Zahradka, P. Aukema, H.M.
Publication Name: J. Nutr.
Publication Details: jn.nutrition.org/content/suppl/2013/08/11/jn.113.17736
Abstract:
Analysis of oxylipins derived from fatty acids may provide insight into the biological effects of dietary lipids beyond their effects on tissue fatty acid profiles. We have previously observed that diets with higher amounts of alpha linolenic acid (ALA; 18:3n3) are associated with reduced obesity-related glomerulopathy (ORG). Therefore, to examine the renal oxylipin profile, the effects of dietary linoleic acid (LA; 18:2n6) and ALA on oxylipins and renal phospholipid fatty acid composition, and the relationship between oxylipins and ORG, diet-induced obese rats displaying ORG were fed 8 different diets for 8 wk as follows (oil/oil equal combination of two oils) [shown as ALA/LA (in g) 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). Targeted lipidomic analysis by HPLC–tandem mass spectrometry revealed that LA and ALA oxylipins comprised 60percent of the total renal oxylipin profile examined. Of the greater than 60 oxylipins screened, only those derived either directly or indirectly from ALA were associated with less glomerulomegaly, indicative of reduced ORG progression. Both the amount and ratio of dietary LA and ALA influenced renal polyunsaturated fatty acids (PUFAs); in contrast, only fatty acid amount altered oxylipins derived from these fatty acids, but there was no apparent competition by LA or ALA on their formation. Dietary LA incorporation into renal phospholipids was higher than for ALA, but ALA oxylipin:ALA ratios were higher than the analogous LA ratios for select lipoxygenase reactions. This indicates that the effect of dietary ALA on renal oxylipins exceeded what was reflected in renal PUFA composition. In conclusion, dietary LA and ALA have differential effects on renal oxylipins and PUFAs, and ALA derived oxylipins are associated with renoprotection in this model of ORG. (Authors abstract)
Oxylipins are oxidized metabolites of fatty acids that can be formed attached to phospholipid or more commonly when fatty acids are released from membrane phospholipids via phospholipase A2, resulting in oxylipins such as the eicosanoids, octadecanoids, and docosanoids. Little knowledge exists on octadecanoids derived from linoleic acid (LA; 18:2n6) and alpha linolenic acid (ALA; 1 18:3n3). Dietary n6 and n3 PUFAs influence the production of oxylipins derived from ARA, EPA, and DHA , but how dietary LA and ALA manipulation affects the amounts of LA and ALA derived oxylipins has yet to be assessed. The ability to alter the oxylipin profile through diet may be particularly important for obese individuals. Obesity may be associated with increased levels of proinflammatory and vasoconstrictive eicosanoids and decreased levels of anti-inflammatory eicosanoids. Oxidative stress, inflammation, and altered hemodynamics in kidneys of obese individuals are associated with the onset of an emerging condition referred to as obesity related glomerulopathy (ORG). The purpose of the current analyses is to report the renal oxylipin lipidomic profile, to evaluate the potential of dietary LA and ALA levels and ratios to modulate this profile, to relate this profile to renal phospholipid fatty acid composition, and to
examine whether oxylipins are associated with glomerulomegaly and disease progression in ORG. The data demonstrate that the LA and ALA oxylipins are present at substantial levels and therefore may have important biological effects. The current analysis demonstrated that the LA and ALA oxylipins can be significantly altered by dietary intervention. If specific oxylipins are shown to be beneficial or detrimental, the potential for dietary modulation to produce an optimal oxylipin profile exists in order to promote health. In this regard, correlation analyses revealed that glomerulomegaly in the diet-induced obese rat was inversely associated with renal
oxylipins derived from ALA, either directly (9 and 13 HOTrE) or indirectly (5 HEPE, 4 HDoHE). In the kidneys from rats fed an HF canola/flax diet, which had similar levels of dietary LA and ALA, LA was 17.7 fold higher than ALA, but HODE was only 3.4 fold higher than HOTrE levels; in addition, ALA and EPA were present at similar levels in these kidneys, but the 5 LOX ALA metabolite (9 HOTrE) was 2-fold higher than the analogous EPA metabolite (5 HEPE). In addition, there were no differences in renal ARA content between any of the diet groups, but there were differences in DHET and HETE levels. Another interesting disconnection between tissue fatty acid and oxylipin levels is that there appeared to be no competition for the formation of oxylipins from longer chain n3 PUFAs by dietary LA. This is in contrast to evidence that higher levels of dietary LA compete with ALA, resulting in lower incorporation of n3 fatty acids in tissues. In conclusion, the current study reported the renal oxylipin profile in the rat and showed that LA and ALA oxylipins are an important component of this profile. This profile was significantly altered by diets containing oils with varying levels of LA and ALA. Four oxylipins derived directly or indirectly from ALA were inversely correlated with glomerulomegaly, suggesting a possible protective effect of these unique oxylipins. The results of the current study show that LA and ALA oxylipins with potentially important biological effects are present in large amounts and are responsive to dietary intervention and that oxylipins (including eicosanoids) may be altered even when tissue fatty acid is not changed. Data on oxylipins, in addition to fatty acid data, are therefore warranted when examining dietary lipid effects on biology. (Editors comments)
examine whether oxylipins are associated with glomerulomegaly and disease progression in ORG. The data demonstrate that the LA and ALA oxylipins are present at substantial levels and therefore may have important biological effects. The current analysis demonstrated that the LA and ALA oxylipins can be significantly altered by dietary intervention. If specific oxylipins are shown to be beneficial or detrimental, the potential for dietary modulation to produce an optimal oxylipin profile exists in order to promote health. In this regard, correlation analyses revealed that glomerulomegaly in the diet-induced obese rat was inversely associated with renal
oxylipins derived from ALA, either directly (9 and 13 HOTrE) or indirectly (5 HEPE, 4 HDoHE). In the kidneys from rats fed an HF canola/flax diet, which had similar levels of dietary LA and ALA, LA was 17.7 fold higher than ALA, but HODE was only 3.4 fold higher than HOTrE levels; in addition, ALA and EPA were present at similar levels in these kidneys, but the 5 LOX ALA metabolite (9 HOTrE) was 2-fold higher than the analogous EPA metabolite (5 HEPE). In addition, there were no differences in renal ARA content between any of the diet groups, but there were differences in DHET and HETE levels. Another interesting disconnection between tissue fatty acid and oxylipin levels is that there appeared to be no competition for the formation of oxylipins from longer chain n3 PUFAs by dietary LA. This is in contrast to evidence that higher levels of dietary LA compete with ALA, resulting in lower incorporation of n3 fatty acids in tissues. In conclusion, the current study reported the renal oxylipin profile in the rat and showed that LA and ALA oxylipins are an important component of this profile. This profile was significantly altered by diets containing oils with varying levels of LA and ALA. Four oxylipins derived directly or indirectly from ALA were inversely correlated with glomerulomegaly, suggesting a possible protective effect of these unique oxylipins. The results of the current study show that LA and ALA oxylipins with potentially important biological effects are present in large amounts and are responsive to dietary intervention and that oxylipins (including eicosanoids) may be altered even when tissue fatty acid is not changed. Data on oxylipins, in addition to fatty acid data, are therefore warranted when examining dietary lipid effects on biology. (Editors comments)
