Effect Of Dietary Linoleic Acid Research Articles

P22-004-23 Effects of Dietary Linoleic Acid on Insulin Resistance and Loss of Adipose Tissue and Skeletal Muscle in a Mouse Model of Cancer Cachexia

P22-004-23 Effects of Dietary Linoleic Acid on Insulin Resistance and Loss of Adipose Tissue and Skeletal Muscle in a Mouse Model of Cancer Cachexia

CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid.

Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since the LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice. Finally, CYP monooxygenase mediates the pro-cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota-dependent mechanisms. Overall, these results support that CYP monooxygenase-mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.

Effects of Dietary Linoleic Acid on Blood Lipid Profiles: A Systematic Review and Meta-Analysis of 40 Randomized Controlled Trials.

Th aim of this meta-analysis was to elucidate whether dietary linoleic acid (LA) supplementation affected blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), compared with other fatty acids. Embase, PubMed, Web of Science and the Cochrane Library databases, updated to December 2022, were searched. The present study employed weighted mean difference (WMD) and a 95% confidence interval (CI) to examine the efficacy of the intervention. Out of the 3700 studies identified, a total of 40 randomized controlled trials (RCTs), comprising 2175 participants, met the eligibility criteria. Compared with the control group, the dietary intake of LA significantly decreased the concentrations of LDL-C (WMD: -3.26 mg/dL, 95% CI: -5.78, -0.74, I2 = 68.8%, p = 0.01), and HDL-C (WMD: -0.64 mg/dL, 95% CI: -1.23, -0.06, I2 = 30.3%, p = 0.03). There was no significant change in the TG and TC concentrations. Subgroup analysis showed that the LA intake was significantly reduced in blood lipid profiles compared with saturated fatty acids. The effect of LA on lipids was not found to be dependent on the timing of supplementation. LA supplementation in an excess of 20 g/d could be an effective dose for lowering lipid profiles. The research results provide further evidence that LA intake may play a role in reducing LDL-C and HDL-C, but not TG and TC.

Effect of Dietary Linoleic Acid (18:2n-6) Supplementation on the Growth Performance, Fatty Acid Profile, and Lipid Metabolism Enzyme Activities of Coho Salmon (Oncorhynchus kisutch) Alevins.

Simple SummaryIn China, coho salmon is becoming an increasing farming species in recent years. Thus, full understanding of the fatty acid requirements of coho salmon is particularly relevant, especially during the larval stage, since they need high-energy demands and rapid lipid metabolism. As a vital essential fatty acid, linoleic acid (18:2n-6) also plays an important role in the larval stage due to the production of longer-chained and more essential highly unsaturated fatty acids (HUFA). However, there is a lack of knowledge about the dietary linoleic acid (18:2n-6) requirement for this fish species. In this study, six isonitrogenous and isolipidic diets were formulated to contain different dietary linoleic acids (18:2n-6) by increasing corn oil at the expense of coconut oil to study the growth performance, fatty acid profile, and hepatic lipid metabolism enzymes of coho salmon alevins. The results showed that the dietary linoleic acid (18:2n-6) affected the growth performance, muscle fatty acid profile, and hepatic lipid metabolism enzyme activities of coho salmon, and determined the optimal demand of linoleic acid based on the specific growth rate (SGR) and feed conversion ratio (FCR).A 12-week feeding trial aimed to evaluate the effects of dietary linoleic acid (LA, 18:2n-6) on the growth performance, fatty acid profile, and lipid metabolism enzyme activities of coho salmon (Oncorhynchus kisutch) alevins. Six experimental diets (47% crude protein and 15% crude lipid) were formulated to contain graded LA levels of 0.11%, 0.74%, 1.37%, 2.00%, 2.63%, and 3.26%. Each diet was fed to triplicate groups of 50 alevins with an initial body weight of 0.364 ± 0.002 g, which were randomly assigned to 18 white plastic tanks (0.8 × 0.6 × 0.6 m, 240 L/tank). Fish were reared in a freshwater flow-through rearing system and fed to apparent satiation four times daily. The survival rate was not significantly different among the treatments (p > 0.05). However, the 1.37% LA group significantly improved the final body weight and specific growth rate (SGR) (p < 0.05) of alevins. The feed conversion ratio (FCR) in the 1.37% LA group was significantly lower than those in other groups (p < 0.05). The whole-body lipid content significantly decreased (p < 0.05) with dietary LA levels increasing from 0.74% to 2.00%. The fatty acid composition of the total lipid in muscle was closely correlated with those in the diets. The dietary LA level of 1.37% led to significantly higher activities of liver lipoprotein lipase (LPL) and hepatic lipase (HL) than those of other groups (p < 0.05). Hepatic malate dehydrogenase (MDH) and fatty acid synthase (FAS) decreased with the increase in the dietary LA levels from 0.11% to 1.37%. The lowest MDH and FAS activities were obtained in the 1.37% LA group (p < 0.05). This study indicated that an appropriate amount of dietary LA was beneficial for the growth and lipid metabolism of coho salmon alevins, and the results of the quadratic regression analysis of the SGR and FCR indicated that the optimal dietary LA requirements were 1.25% and 1.23% for coho salmon alevins, respectively.

The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apoE-deficient mice.

Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE-/-) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups (P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions (P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE-/- mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis.

Evaluation of dietary linoleic acid on growth as well as hepatopancreatic index, lipid accumulation oxidative stress and inflammation in Chinese mitten crabs (Eriocheir sinensis)

This study aimed to investigate the effect of dietary linoleic acid (LA) on the growth, hepatopancreatic development and health of Eriocheir sinensis. Crabs (initial body weight: 28.53 ± 0.63 g) were fed with five formulated diets containing graded levels of LA (7, 14, 21, 28, 35 g/kg) for 90 days. Each diet was tested in four replicates. A significant (P < 0.05) increase in weight gain (WG) and specific growth rate (SGR) was observed as dietary LA levels vary 21–35 g/kg. 21 or 28 g/kg dietary LA promoted hepatopancreatic development, which was evidenced by an increased (P < 0.05) hepatopancreatic index (HSI) and decreased (P < 0.05) proportion of G2/M cells. Immunofluorescence analysis showed that the accumulation of hepatopancreatic lipid increased (P < 0.05) in 21 and 28 g/kg LA groups. These effects possibly were associated with increased (P < 0.05) expression of CPT1, ACO, FATP 4, FABP10 and FAS. In addition, increased (P < 0.05) malondialdehyde (MDA) and suppressed (P < 0.05) total antioxidant capacity (T-AOC) was observed in E. sinensis fed with 28 or 35 28 g/kg dietary LA. The expression of genes related to inflammation showed no significant difference among all groups. In conclusion, 21 or 28 g/kg dietary LA promoted growth, HSI and the accumulation of hepatopancreatic lipid; High-grade dietary LA (28 and 35 g/kg) did not induce inflammation and inhibit growth but posed a threat to oxidative stress.

Effects of parental dietary linoleic acid on growth performance, antioxidant capacity, and lipid metabolism in domestic pigeons (Columba livia)

The objective of this study was to evaluate the effects of dietary linoleic acid (LA) on growth performance, antioxidant capacity, and lipid metabolism in pigeon squabs by supplementing LA in their parental diets. A completely randomized design that consisted of a control group, 1% dietary LA addition group (LA1%), 2% dietary LA addition group (LA2%), and 4% dietary LA addition group (LA4%) was used. Six squabs from each treatment were randomly sampled at the day of hatch and days 7, 14, and 21 after hatch. The results showed that parental dietary LA had no significant influence (P > 0.05) on body weight (BW) gain or relative organ weights (% of BW) in squabs. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the LA1% were significantly increased (P < 0.05) compared with those in the control group. The malondialdehyde content in the LA1% was significantly lower (P < 0.05) than that in the control group. The levels of serum triglyceride in the LA1% and LA2% were significantly decreased (P < 0.05) compared with those in the control group, whereas the serum high-density lipoprotein cholesterol level in the LA1% and LA2% and the free fatty acid level in the LA4% were significantly higher (P < 0.05) than those of the control group. The activities of lipoprotein lipase, hepatic lipase, and hormone-sensitive lipase in the LA1% were significantly higher (P < 0.05) than those in the control group. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the LA1% and the hormone-sensitive lipase activity in the LA4% were significantly decreased (P < 0.05) compared with those in the control group. The mRNA expression of carnitine palmitoyltransferase 1, acyl-CoA 1, and peroxisome proliferator-activated receptor α was significantly upregulated (P < 0.05) in the LA1% compared with that in the control group. The Oil Red O staining area in the LA1% and LA2% was significantly reduced compared with that in the control group. The results indicated that although supplemental LA had negligible effects on growth and development in pigeon squabs, parental dietary LA at a concentration of 1% could have beneficial effects on maintaining squabs healthy as reflected by improved antioxidant capacity and lipid metabolism.

The effects of dietary linoleic acid and hydrophilic antioxidants on basal, peak, and sustained metabolism in flight-trained European starlings.

Dietary micronutrients have the ability to strongly influence animal physiology and ecology. For songbirds, dietary polyunsaturated fatty acids (PUFAs) and antioxidants are hypothesized to be particularly important micronutrients because of their influence on an individual's capacity for aerobic metabolism and recovery from extended bouts of exercise. However, the influence of specific fatty acids and hydrophilic antioxidants on whole‐animal performance remains largely untested. We used diet manipulations to directly test the effects of dietary PUFA, specifically linoleic acid (18:2n6), and anthocyanins, a hydrophilic antioxidant, on basal metabolic rate (BMR), peak metabolic rate (PMR), and rates of fat catabolism, lean catabolism, and energy expenditure during sustained flight in a wind tunnel in European starlings (Sturnus vulgaris). BMR, PMR, energy expenditure, and fat metabolism decreased and lean catabolism increased over the course of the experiment in birds fed a high (32%) 18:2n6 diet, while birds fed a low (13%) 18:2n6 diet exhibited the reverse pattern. Additionally, energy expenditure, fat catabolism, and flight duration were all subject to diet‐specific effects of whole‐body fat content. Dietary antioxidants and diet‐related differences in tissue fatty acid composition were not directly related to any measure of whole‐animal performance. Together, these results suggest that the effect of dietary 18:2n6 on performance was most likely the result of the signaling properties of 18:2n6. This implies that dietary PUFA influence the energetic capabilities of songbirds and could strongly influence songbird ecology, given their availability in terrestrial systems.

Optimal dietary linoleic acid to linolenic acid ratio improved fatty acid profile of the juvenile tambaqui (Colossoma macropomum)

The present study aimed to evaluate the effect of dietary linoleic acid to linolenic acid (LNA/ALA) ratio on growth performance, feed utilization, plasma metabolite profiles, and muscle and liver fatty acid profiles of juvenile tambaqui Colossoma macropomum. Six diets were formulated to contain incremental levels of corn oil (rich in LNA) from 0 to 7% at the expense of linseed oil (rich in ALA), resulting in dietary LNA/ALA ratios ranging from 3.1 to 26.9. A control diet including fish oil was also formulated. The trial lasted 49 days, and each diet was assigned to six groups of fish with an initial body weight of 43 g. At the end of the trial, dietary LNA/ALA ratio did not affect growth performance, feed utilization, and plasma metabolites profile, except for HDL that was lower in fish fed the 3.8 LNA/ALA diet than the 3.1 or 5.0 LNA/ALA diets. Whole-body protein content was lower in fish fed the control and 3.1 LNA/ALA diets. Composition of triglycerides, glucose and protein of liver and muscle was unaffected by dietary treatments. Eicosapentaeneoic acid (EPA, 20:5n–3) plus docosahexaenoic acid, (DHA, 22:6n–3) content of muscle decreased with the increase of LNA/ALA ratio. Fish fed 3.9–5.6 LNA/ALA diet showed the highest concentration of muscle ARA (arachidonic acid, 20:4n-6) and EPA + DHA among vegetable oil diets, though lower than that of fish fed the fish oil based diet. In conclusion, dietary LNA/ALA ratio should range between 3.9–5.6 to produce fillets with high EPA, DHA, and ARA contents, thus improving the nutritional quality of tambaqui fillets for human consumers.

Linoleic Acid: A Nutritional Quandary.

Over the course of the twentieth century, there was a 20-fold increase in consumption of vegetable oils resulting both from their increased availability and from recommendations to consume these oils as an aid to lower blood cholesterol levels. This dietary change markedly increased the consumption of linoleic acid to current levels of approximately 6% of total dietary energy. While considerable research has focused on the effects of dietary linoleic acid on cardiovascular health, questions about optimum dietary levels remain. For example, meta-analyses disagree about the role of dietary linoleic acid in atherosclerosis, and recent publications indicate that linoleic acid’s reduction of blood cholesterol levels does not predict its effect on the development of atherosclerosis. Further, there are also detrimental effects of elevated dietary linoleic acid on human health related to its role in inflammation and its activity as a promoter of cancer in animals. Current data do not allow determination of the level of dietary linoleic acid needed for optimum health. Studies of the effects of a wide range of linoleic acid consumption may help determine dietary recommendations that are optimal for human health.

Dietary Linoleic Acid and α-Linolenic Acid Differentially Affect Renal Oxylipins and Phospholipid Fatty Acids in Diet-Induced Obese Rats

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 α-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 = 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 60% of the total renal oxylipin profile examined. Of the >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.

Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials

The majority of evidence suggests that n-6 polyunsaturated fatty acids, including linoleic acid (LA), reduce the risk of cardiovascular disease as reflected by current dietary recommendations. However, concern has been expressed that a high intake of dietary n-6 polyunsaturated fatty acid contributes to excess chronic inflammation, primarily by prompting the synthesis of proinflammatory eicosanoids derived from arachidonic acid and/or inhibiting the synthesis of anti-inflammatory eicosanoids from eicosapentaenoic and/or docosahexaenoic acids. A systematic review of randomized controlled trials that permitted the assessment of dietary LA on biologic markers of chronic inflammation among healthy noninfant populations was conducted to examine this concern. A search of the English- and non–English-language literature using MEDLINE, the Cochrane Controlled Trials Register, and EMBASE was conducted to identify relevant articles. Fifteen studies (eight parallel and seven crossover) met inclusion criteria. None of the studies reported significant findings for a wide variety of inflammatory markers, including C-reactive protein, fibrinogen, plasminogen activator inhibitor type 1, cytokines, soluble vascular adhesion molecules, or tumor necrosis factor-α. The only significant outcome measures reported for higher LA intakes were greater excretion of prostaglandin E2 and lower excretion of 2,3-dinor-thromboxane B2 in one study and higher excretion of tetranorprostanedioic acid in another. However, the authors of those studies both observed that these effects were not an indication of increased inflammation. We conclude that virtually no evidence is available from randomized, controlled intervention studies among healthy, noninfant human beings to show that addition of LA to the diet increases the concentration of inflammatory markers.

Systematic review of the effect of dietary linoleic acid on changes of tissue levels of arachidonic acid and docosahexaenoic acid in humans

Linoleic acid (LA), with a DRI of 11–17g/d, is the most commonly consumed polyunsaturated fatty acid (PUFA) in the Western diet. The concern is that LA is the metabolic precursor of arachidonic acid (AA) and its consumption may enrich tissues with AA and contribute to chronic and overproduction of bioactive eicosanoids derived from AA. Similarly, there is a concern that dietary LA may interfere with the production and incorporation of the long chain n‐3 PUFA into tissues, in particular, docosahexaenoic acid (DHA). However, no systematic review of human trials regarding LA consumption and subsequent changes in tissue levels of AA or DHA has been undertaken. In this study, we systematically reviewed the human literature that reported changes in dietary LA and its subsequent impact on changing tissue AA and/or DHA in platelets, erythrocytes and plasma phospholipids. Decreasing dietary LA up to 90% failed to modify tissue AA levels (p=0.39). When dietary LA levels were increased 6 fold, no changes in tissue AA levels were observed (p=0.72). Similarly, decreasing (by 90%) or increasing (6 fold) dietary LA failed to modify tissue DHA levels (p=0.39 and p=0.55, respectively). Our results suggest that modifying current intakes of dietary LA have no effect on changing tissue levels of AA or DHA in adults. (Supported, in part, by the TN AES and in conjunction with USDA's NC‐1039 multistate research project).

Physiological effects of dietary linoleic acid.

Physiological effects of dietary linoleic acid.

Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements

There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation - chain elongation pathway.

Effect of dietary linoleic acid on the progression of chronic renal failure in rats.

The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean +/- SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 +/- 4 vs 126 +/- 13 mg%) and triglyceride (88 +/- 9 vs 132 +/- 19 mg%) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78% in RS and 100% in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27%) compared to RN (38%), tubulointerstitial damage was similar between CRF groups (RS = 1.91 +/- 0.2 and RN = 2.14 +/- 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days.

Eicosanoids as mediators of linoleic acid-stimulated invasion and type IV collagenase production by a metastatic human breast cancer cell line

Diets rich in linoleic acid (LA) stimulate the metastasis of MDA-MB-435 human breast cancer cells from the mammary fat pads of nude mice. This omega-6 fatty acid is metabolized to various cyclo-oxygenase and lipoxygenase products, several of which have been previously associated with tumor cell invasion and metastasis. We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2), and 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE when cultured in the presence of 2.7 microM (0.75 micrograms/ml) LA; 5-HETE secretion was unchanged. The 12-lipoxygenase inhibitor esculetin (20 microM) completely blocked the LA-stimulated 12-HETE secretion. Linoleic acid also increased MDA-MB-435 cell invasion in an in vitro assay; this stimulation was abolished by 20 microM esculetin, but was unaffected by piroxicam, a selective cyclooxygenase inhibitor. The effect of LA on invasion was replicated by 0.1 microM 12-HETE, but not by 5-HETE or PGE2; 15-HETE was stimulatory only at a concentration of 1.0 microM. Zymographic and Northern blot analyses showed that these events are accompanied by the induction of 92 kDa isoform type IV collagenase (metalloproteinase-9) enzymic activity and mRNA expression by exogenous LA and 12-HETE, and their suppression by the 12-lipoxygenase inhibitor. These results suggest that the effects of dietary LA on breast cancer cell metastasis in the nude mouse model are due, at least in part, to enhanced 12-HETE biosynthesis, with an associated increase in proteolytic enzyme activity and tumor cell invasiveness.

Effect of dietary linoleic acid on the tryptophanniacin metabolism in streptozotocin diabetic rats

To make clear the mechanism of change of tryptophan-niacin metabolism in diabetic rats, we investigated the effect of dietary linoleic acid on the tryptophan-niacin metabolites and the activity of liver, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of tryptophan-niacin metabolism, in streptozotocin diabetic rats. Moreover, we investigated the involvement of linoleic acid in the induction of hepatic ACMSD activity by streptozotocin diabetes. In diabetic rats, the sum of urinary excretion of nicotinamide, N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py) and N1-methyl-4-pyridone-3-carboxamide (4-Py) was higher in the fat free diet group than in the linoleic acid group, that was accompanied by the increase of tryptophan intake and reduction of body weight in the fat free diet group. In diabetic rats, hepatic ACMSD activity was higher in the fat free diet group than in the linoleic acid group. The results indicated that the induction of hepatic ACMSD activity by diabetes was not due to removal of the suppressive effect of the linoleic acid on the enzyme. In the diabetic+insulin group, hepatic ACMSD activity was significantly lower than in the diabetic group.

Effect of dietary linoleic acid content on the distribution of phosphatidylcholine molecular species in rat plasma

The effect of dietary linoleic acid on the profiles of phosphatidylcholine molecular species in rat plasma was investigated. On changing from an essential fatty acid-deficient state to an essential fatty acid sufficient state, the levels of molecular species containing 18:1 and 20:3n−9 were decreased, whereas those containing 18:2n−6 and 20:4n−6 were increased. However, the decrease was greater in the molecular species containing 20:3n−9 than in those containing 18:1, and the increase was greater in the molecular species containing 20:4n−6 than in those containing 18:2n−6. In rats fed the essential fatty acid deficient diet (containing 0.001 g/kg diet of linoleic acid), the major molecular species in plasma phosphatidylcholine was 16:0–8:1 and most of the molecular species have the total carbon chain length around 34. In rats fed the essential sufficient diet (containing 2.4 g/kg diet of linoleic acid), the major phosphatidylcholine molecular species was 18:0–20:4n−6, and most species had the total carbon chain length around 38. The changes of the molecular species profiles indicated that the metabolism of 18:1 to 20:3n−9 which was active in the essential fatty acid deficient rats was replaced with that of 18:2n−6 to 20:4n−6 in the essential fatty acid sufficient state.

Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males

The purpose of this study was to investigate the effect of dietary linoleic acid (18:2( n − 6)) on the conversion of 18:2( n − 6) and 18:3( n − 3) to their respective n − 6 and n − 3 metabolites; to compare the incorporation of these fatty acids into human plasma lipids; to evaluate the importance of dietary 18:3( n − 3) as a precursor for the biosynthesis of long-chain length n − 3 fatty acids. The approach used was to feed young adult male subjects ( n = 7) diets containing 2 levels of linoleic acid (SAT diet, 15 g/day; PUFA diet, 30 g/day) for 12 days. A mixture of triacylglycerols containing deuterated linolenic (18:3( n − 3)) and linoleic (18:2( n − 6)) acids was fed and blood samples were drawn over a 48 h period. Concentrations of deuterated 18:3( n − 3) in plasma total lipid ranged from 309.2 to 606.4 μg/ml and concentrations of 18:2( n − 6) ranged from 949.2 to 1743.3 μg/ml. The sum of the deuterated n − 3 long-chain length fatty acid metabolites in plasma total lipid were 116 ± 4.3 μg/ml (SAT diet) and 41.6 ± 12.4 jug/ml (PUFA diet). The total deuterated n − 6 fatty acid metabolites were 34.6 ± 12.2 μg/ml (SAT diet) and 9.8 ± 5.9 μg/ml (PUFA diet). The total percent conversion of deuterated 18:3( n − 3) to n − 3 fatty acid metabolites and deuterated 18:2( n − 6) to n − 6 fatty acid metabolites were 11–18.5% and 1.0–2.2%, respectively. The percentages for deuterated 20:5( n − 3), 22:5( n − 3) and 22:6( n − 3) (6.0%, 3.5%, and 3.8%) were much higher than for 20:3( n − 6) and 20:4( n − 6) (0.9% and 0.5%). Overall, conversion of deuterated 18:3( n − 3) and 18:2( n − 6) was reduced by 40–54% when dietary intake of 18:2( n − 6) was increased from 15 to 30 g/day. Comparison of the deuterated 18:3( n − 3) and 18:2( n − 6) data for plasma triacylglycerol and phosphatidylcholine (PC) indicated that 18:2( n − 6) was preferentially incorporated into PC. Dietary 18:2( n − 6) intake did not alter acyltransferase selectivity but activity was reduced when 18:2( n − 6) intake was increased. Based on these results, conversion of the 18:3( n − 3) in the US diet (2 g) is estimated to provide 75–85% of the long-chain length n − 3 fatty acids needed to meet daily requirements for some (but not all) adults.