Linoleic Diet Research Articles

Greater oxidation of dietary linoleate compared to palmitate in humans following an acute high-carbohydrate diet

We have previously demonstrated that dietary saturated fatty acids (SFA), when compared to polyunsaturated fatty acids (PUFA), are preferentially partitioned into oxidation pathways. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated. To investigate whether an acute upregulation of hepatic DNL influences dietary FA partitioning into oxidation pathways. 20 healthy volunteers (11 females) underwent a fasting baseline visit followed by two study days, 2-weeks apart. Prior to each study day, participants consumed an isocaloric high-carbohydrate diet (to upregulate hepatic DNL) for 3-days. On the two study days, participants consumed an identical standardised test meal that contained either [U13C]palmitate or [U13C]linoleate, in random order, to trace the fate of dietary FA. Blood and breath samples were collected over a 6h postprandial period and 13C enrichment in breath CO2 and plasma lipid fractions were measured using gas-chromatography-combustion-isotope ratio mass spectrometry. Compared to the baseline visit, fasting plasma triglyceride concentrations and markers of hepatic DNL, the lipogenic and stearyl-CoA desaturase indices, were significantly (p<0.05) increased after consumption of the high-carbohydrate diet. Appearance of 13C in expired CO2 and tracer recovery were significantly (p<0.05) higher after consumption of the meal containing [U13C]linoleate compared to [U13C]palmitate (5.1±0.5% vs. 3.7±0.4%), respectively. Incorporation of 13C into the plasma triglyceride and non-esterified fatty acid pool was significantly (p<0.001) greater for [U13C]palmitate compared to [U13C]linoleate. Dietary PUFA compared to SFA appear to be preferentially partitioned into oxidation pathways during an acute upregulation of hepatic DNL, thus consumption of a PUFA-enriched diet may help mitigate intrahepatic triglyceride accumulation in individuals at risk of cardiometabolic disease.

The influence of nutritional state on the fatty acid composition of circulating lipid fractions: implications for their use as biomarkers of dietary fat intake.

BackgroundThe fatty acid (FA) composition of blood can be used as an objective biomarker of dietary FA intake. It remains unclear how the nutritional state influences the FA composition of plasma lipid fractions, and thus their usefulness as biomarkers in a non-fasted state.ObjectivesTo investigate the associations between palmitate, oleate and linoleate in plasma lipid fractions and self-reported dietary FA intake, and assess the influence of meal consumption on the relative abundance of these FA in plasma lipid fractions (i.e. triglyceride [TG], phospholipids [PLs] and cholesterol esters [CEs]).DesignAnalysis was performed in plasma samples collected from 49 (34 males and 15 females) participants aged 26–57 years with a body mass index (BMI) between 21.6 and 34.2 kg/m2, all of whom had participated in multiple study visits, thus a pooled cohort of 98 data sets was available for analysis. A subset (n = 25) had undergone nutritional interventions and was therefore used to investigate the relationship between the FA composition of plasma lipid fractions and dietary fat intake.ResultsSignificant (P < 0.05) positive associations were observed between dietary polyunsaturated fat and linoleate abundance in plasma CE. When investigating the influence of meal consumption on postprandial FA composition, we found plasma TG palmitate significantly (P < 0.05) decreased across the postprandial period, whereas oleate and linoleate increased. A similar pattern was observed in plasma PL, whereas linoleate abundance decreased in the plasma CE.ConclusionOur data demonstrate that the FA composition of plasma CE may be the lipid fraction to utilise as an objective biomarker when investigating recent (i.e. previous weeks-months) dietary FA intakes. In addition, we show that the consumption of a high-fat meal influences the FA composition of plasma TG, PL and CE over the course of the postprandial period, and therefore, suggest that fasting blood samples should be utilised when using FA composition as a biomarker of dietary FA intake.

204 An Investigation into the Role of Dietary Essential Fatty Acids Ratios and Linoleic Acid Level on Growth Performance and Inflammation of Grow-finish Pigs

Abstract The objective was to investigate the effects of dietary linoleic acid level and the ratio of linoleic acid:linolenic acid (n6:n3) on the growth performance and inflammatory status of grow-finish pigs. A total of 300 growing pigs (BW = 41.1 ± 6.3 kg) were randomly assigned to either a high (30 g/kg; HLA) or low (15 g/kg; LLA) linoleic acid level with a high (20:1; HR), moderate (12:1; MR) or low (4:1; LR) n6:n3 in a 2 x 3 factorial design. Diets were fed across three 28-day phases and were balanced for dietary metabolizable energy. Pigs were housed 5 pigs per pen. Blood samples were collected on weeks 1, 3, 6, and 12, and synovial fluid was collected from the hock joint on weeks 1 and 12 for inflammatory marker analysis. Data were analyzed as repeated measures using PROC MIXED (SAS 9.4) with initial body weight as a covariate, pen as the experimental unit, and linoleic acid level, ratio, and their interaction as fixed effects. Compared to HLA, LLA pigs had increased BW (P &amp;lt; 0.05) at d56 (103.2 vs. 101.3kg) and tended to have increased BW at d84 (P &amp;lt; 0.10; 129.1 vs. 127.8kg). Pigs receiving LR tended to have higher d84 BW compared to MR (P &amp;lt; 0.10; 129.1 vs. 127.3kg). There was no effect of linoleic acid ratio interaction for growth performance. In phase 2, pigs receiving LR had higher feed intake (P &amp;lt; 0.05) compared to MR. Pigs receiving HR performed intermediate of LR and MR. Overall, C-reactive protein was reduced in the plasma of pigs receiving HLA (P &amp;lt; 0.05; 19.3 vs. 26.2mg/mL). Across all treatments, CRP was reduced in synovial fluid and plasma in week 12 vs. week 1 (P &amp;lt; 0.05). In conclusion, LLA and a low ratio of n6:n3 improved final pig BW, and HLA is potentially beneficial in improving inflammation.

Oxidation of dietary linoleate occurs to a greater extent than dietary palmitate in vivo in humans

It has been suggested that dietary polyunsaturated fatty acids (PUFA) are partitioned into oxidation pathways to a greater extent than dietary saturated fatty acids (SFA). Whilst this has been demonstrated in animal models, evidence in humans is lacking. The potential divergence in the metabolic fate of these dietary fatty acids (FA) may explain some of the reported differences in ectopic fat deposition with SFA and PUFA enriched diets. To compare whole-body oxidation of dietary palmitate and linoleate after consumption of a single test meal. In a randomized, crossover design 24 healthy volunteers (12 males and 12 females, matched for age and BMI) underwent two study days separated by 2-week washout period. During each study day participants consumed a standardized test meal which contained [U13C]palmitate or [U13C]linoleate. Blood and breath samples were collected over the 6h postprandial period and the 13C enrichment in breath CO2 samples and plasma lipid fractions was determined. Appearance of 13C in expired CO2 was significantly (p<0.05) increased after consumption of the meal containing [U13C]linoleate compared to the meal containing [U13C]palmitate. The recovery of tracer was 8.9±1.2% [U13C]linoleate vs. 5.6±0.4% [U13C]palmitate (p<0.05). The incorporation of 13C from [U13C]palmitate was greater in plasma triacylglycerol and non-esterified fatty acids than [U13C]linoleate, whereas the incorporation of 13C from [U13C]linoleate was greater than [U13C]palmitate in plasma phospholipids. Although 13CO2 was significantly (p<0.05) higher in females compared to males after consumption of [U13C]palmitate, there was no difference in 13CO2 between sexes after consumption of [U13C]linoleate. We demonstrate that whole-body oxidation of dietary linoleate is comparatively higher than that of dietary palmitate in humans following consumption of a single mixed-test meal. We found indications of sexual dimorphism for dietary palmitate but not dietary linoleate. http://www.clinicaltrials.org/ ID number NCT03587753.

Linoleate-enriched diet increases both linoleic acid esterified to omega hydroxy very long chain fatty acids and free ceramides of canine stratum corneum without effect on protein-bound ceramides and skin barrier function

Few studies have investigated the influence of increased amounts of dietary linoleic acid on the epidermal lipid biochemistry and TEWL in healthy subject. The influence of dietary linoleic acid on canine stratum corneum (SC) lipids was studied by feeding two groups of five dogs differential amounts of linoleic acid (LA) for three months. SC was harvested by tape stripping and lipids were analyzed by thin-layer chromatography and mass spectrometry. The dogs that were fed the higher concentration of LA showed high increases in the contents of both linoleic acid and free ceramides in the SC, whereas the protein-bound ceramide content was unchanged. Acylacids that represent the esterified form of linoleic acid in omega hydroxy very long chain fatty acids (ω-OH VLCFA) accounted for most of the elevation of LA, whereas the concentration of the free form was not significantly changed. Corroborating the absence of change in the protein-bound ceramides content of healthy dogs SC, TEWL was nearly unaffected by the linoleic acid-enriched diet.

Linoleic and docosahexaenoic acids in human milk have opposite relationships with cognitive test performance in a sample of 28 countries

Polyunsaturated fatty acids play critical roles in brain development and function, and their levels in human breast milk closely reflect the long-term diet. The fatty acid contents of human milk samples from 28 countries were used to predict averaged 2009 and 2012 test scores in mathematics, reading, and science from the Program for International Student Assessment. All test scores were positively related to milk docosahexaenoic acid (r=0.48 to 0.55), and negatively related to linoleic acid (r=−0.28 to −0.56). Together, these two human milk fatty acids explained 46% to 48% of the variance in scores, with no improvement in predictive power when socioeconomic variables were added to the regression. The (log) ratio of linoleic to arachidonic acid was negatively related to scores (r=−0.45 to −0.48). Statistical effects were similar for the two sexes. In a separate US sample, estimated dietary linoleic was negatively related to the levels of all long-chain n-3 and n-6 plasma fatty acids. High levels of dietary linoleic may impair cognition by decreasing both docosahexaenoic and arachidonic acids in the brain.

Is there an optimal dose for dietary linoleic acid? Lessons from essential fatty acid deficiency supplementation and adipocyte functions in rats

Differential effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been demonstrated on adipose tissue physiology. Facing to the widely recognized beneficial effects of n-3 PUFAs, the n-6 PUFA effects remain controversial. Thus, we further analyzed the linoleic acid (LA) influence on adipocyte functions. To this aim, we treated by LA supplementation at three distinct doses (1, 2.5, or 5% of energy intake) rats with essential fatty acids deficiency (EFAD). PUFA composition was determined in blood and white adipose tissue (WAT), while lipolytic and lipogenic activities were measured in isolated adipocytes. EFAD rats exhibited reduced WAT mass and increased EFAD biomarkers. WAT mass was completely recovered after supplementation, irrespective of LA dose. However, neither body mass nor EFAD biomarkers returned to control with 1% LA, while LA abundance doubled in adipocytes from rats supplemented with 5% LA. Regarding lipolysis, 2.5% LA normalized the EFAD-induced alterations. A trend to decrease the maximal stimulation of lipolysis was observed with 1 and 5% LA. Regarding lipogenesis, the lower and higher LA doses increased basal activity and hampered insulin to further stimulate glucose incorporation into lipids whereas 2.5% LA normalized the basal or insulin-stimulated levels. Our results show that dietary linoleate at 2.5% restored anatomical, biochemical, and functional disturbances induced by EFAD. At higher dose, LA tended to reduce triacylglycerol breakdown, to increase triacylglycerol assembly, and to provoke insulin resistance. Therefore, LA influence on adipocyte functions does not appear to follow a typical dose-response relationship, adding further complexity to the definition of its dietary requirement.

Growth performance, meat quality and Fatty Acid metabolism response of growing meat rabbits to dietary linoleic Acid.

An experiment was conducted to determine the effects of different amounts of dietary linoleic acid (LA) on growth performance, serum biochemical traits, meat quality, fatty acids composition of muscle and liver, acetyl-CoA carboxylase (ACC) and carnitine palmitoyl transferase 1 (CPT 1) mRNA expression in the liver of 9 wks old to 13 wks old growing meat rabbits. One hundred and fifty 9 wks old meat rabbits were allocated to individual cages and randomly divided into five groups. Animals in each group were fed with a diet with the following LA addition concentrations: 0, 3, 6, 9 and 12 g/kg diet (as-fed basis) and LA concentrations were 0.84, 1.21, 1.34, 1.61 and 1.80% in the diet, respectively. The results showed as follows: the dietary LA levels significantly affected muscle color of LL included a* and b* of experimental rabbits (p<0.05). The linear effect of LA on serum high density lipoprotein cholesterol was obtained (p = 0.0119). The saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) contents of LL decreased and the polyunsaturated fatty acids (PUFAs) content of LL increased with dietary LA increase (p<0.0001). The PUFA n-6 content and PUFA n-3 content in the LL was significantly affected by the dietary LA levels (p<0.01, p<0.05). The MUFAs content in the liver decreased and the PUFAs contents in the liver increased with dietary LA increase (p<0.0001). The PUFA n-6 content and the PUFA n-6/n-3 ratio in the liver increased and PUFA n-3 content in the liver decreased with dietary LA increase (p<0.01). The linear effect of LA on CPT 1 mRNA expression in the liver was obtained (p = 0.0081). In summary, dietary LA addition had significant effects on liver and muscle fatty acid composition (increased PUFAs) of 9 wks old to 13 wks old growing meat rabbits, but had little effects on growth performance, meat physical traits and mRNA expression of liver relative enzyme of experimental rabbits.

Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart

Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L(4)CL). A selective loss of L(4)CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L(4)CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L(4)CL and total CL to 90% of non-failing levels (vs. 61-75% in control and lard groups), and attenuated 17-22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition.

Maintenance of Arachidonic Acid and Evidence of Δ5 Desaturation in Cats Fed γ‐Linolenic and Linoleic Acid Enriched Diets

Cats have limited Δ6 desaturase activity. However, γ-linolenate (GLA) feeding may by-pass the Δ6 desaturase step allowing arachidonate (ARA) accumulation via Δ5-desaturation. Alternatively, high dietary linoleate (LNA) may induce limited Δ6 desaturase also resulting in ARA accumulation. Fatty acid profiles were determined after feeding high LNA, high GLA, or adequate LNA diets. Adult female cats (n=29) were assigned to one of three groups and fed for 8weeks. Plasma samples were collected at weeks 0, 2, 4 and 8 for plasma triacylglycerol (TAG), total cholesterol (TC), lipoprotein (LP), and plasma and red blood cell membrane phospholipid fatty acid determinations. Time, but no diet, effects were observed for TAG, TC, and LP fractions at weeks 2 and 4 with significant increases likely due to increased dietary fat. However, all values were within feline normal limits. The GLA diet resulted in increased dihomo-γ-linolenic acid (DGLA) and ARA as early as week 2, supporting a ∆5 desaturase. Further evidence of Δ5 desaturase was found at high dietary LNA with the appearance of a novel fatty acid, 20:3 ∆7, 11, 14, apparently formed via ∆5 desaturation and chain elongation of LNA. However, Δ6 desaturase induction at high dietary LNA concentration was not observed. Cats are able to maintain plasma and red blood cell ARA when fed a practical diet containing GLA using what appears to be an active Δ5 desaturase enzyme.

Oxidation of Dietary Stearic, Oleic, and Linoleic Acids in Growing Pigs Follows a Biphasic Pattern ,

We used the pig as a model to assess the effects of dietary fat content and composition on nutrient oxidation and energy partitioning in positive energy balance. Pigs weighing 25 kg were assigned to either: 1) a low fat–high starch diet, or 2) a high saturated-fat diet, or 3) a high unsaturated-fat diet. In the high-fat treatments, 20% starch was iso-energetically replaced by 10.8% lard or 10.2% soybean oil, respectively. For 7 d, pigs were fed twice daily at a rate of 1200 kJ digestible energy · kg-0.75· d-1. Oral bolus doses of [U-13C] glucose, [U-13C] a-linoleate, [U-13C] stearate, and [U-13C] oleate were administered on d 1, 2, 4, and 6, respectively, and13CO2production was measured. Protein and fat deposition were measured for 7 d. Fractional oxidation of fatty acids from the low-fat diet was lower than from the high-fat diets. Within diets, the saturated [U-13C] stearate was oxidized less than the unsaturated [U-13C] oleate and [U-13C] linoleate. For the high unsaturated-fat diet, oxidation of [U-13C] oleate was higher than that of [U-13C] linoleate. In general, recovery of13CO2from labeled fatty acids rose within 2 h after ingestion but peaked around the next meal. This peak was induced by an increased energy expenditure that was likely related to increased eating activity. In conclusion, oxidation of dietary fatty acids in growing pigs depends on the inclusion level and composition of dietary fat. Moreover, our data suggest that the most recently ingested fatty acids are preferred substrates for oxidation when the direct supply of dietary nutrients has decreased and ATP requirements increase.

Abstract 2878: Dietary stearate inhibits tumor development and tumor burden in the N-nitroso-N-methylurea (NMU) rat breast cancer carcinogen model

Abstract The goal of the present study was to test the effectiveness of dietary stearate at inhibiting breast cancer development in a carcinogen induced breast cancer model. Three diets were used; a 17% stearate diet, the key being that highly purified stearate was added directly to the diet, a linoleate diet (SF) containing 17% safflower oil as the source of linoleate and a low fat control diet (LF) with a reduced amount of fat (5%) from corn oil. All three diets had adequate essential fatty acids. These 3 diets were initiated 1 week prior to the rats receiving NMU and followed out 100 days. There was no difference in the weight of the rats among groups throughout the study. Approximately 40% fewer animals on the stearate and safflower diets developed palpable tumors compared to the LF (n=30-35 animals/diet; p&amp;lt;0.05). No difference was observed among the three diets as to the time for first tumor appearance. Stearate decreased the average number of tumors per rat compared to the LF (n=30-35 animals per diet; p&amp;lt;0.05) and had less tumors per rat than the SF although this was not statistically significant. Stearate also significantly reduced tumor burden as defined by tumor weight by ∼50% compared to LF and SF (p&amp;lt;0.001) and large tumors compared to the LF (∼47% reduction in tumors over 0.25 g, p= 0.02). In those rats that did develop tumors, the stearate diet group had a similar number of adenocarcinomas compared to other diets; however the stearate and SF groups had lower numbers of DCIS/microinvasive disease as compared to the LF. The dietary groups tended to have similar numbers of the other precursor lesions classified although the dietary stearate group had the least number of “tubular adenomas”. Dietary stearate may be useful as an alternative/complementary therapy or preventative agent against breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2878.

Dietary palmitate and linoleate oxidations, oxidative stress, and DNA damage differ according to season in mouse lemurs exposed to a chronic food deprivation

This study investigated the extent to which the increase in torpor expression in the grey mouse lemur, due to graded food restriction, is modulated by a trade-off between a whole body sparing of polyunsaturated dietary fatty acids and the related oxidative stress generated during daily torpor. We measured changes in torpor frequency, total energy expenditure (TEE), linoleate (polyunsaturated fatty acid) and palmitate (saturated fatty acid) oxidation, hexanoyl-lysine (HEL; the product of linoleate peroxidation), and 8-hydroxydeoxyguanosine (8OHdG; a marker of DNA damage). Animals under summer-acclimated long days (LD) or winter-acclimated short days (SD) were exposed to a 40% (LD40 and SD40) and 80% (LD80 and SD80) 35-day calorie restriction (CR). During CR, all groups reduced their body mass, but LD80 animals reached survival-threatened levels at day 22 and were then excluded from the CR trial. Only SD mouse lemurs increased their torpor frequency with CR and displayed a decrease in their TEE adjusted for fat-free mass. After CR, SD40 mouse lemurs shifted the dietary fatty acid oxidation toward palmitate and spared linoleate. Such a shift was not observed in LD animals and during severe CR, during which oxidation of both dietary fatty acids was increased. Concomitantly, HEL increased in both LD40 and SD80 groups, whereas DNA damage was only seen in SD80 food-restricted animals. HEL correlated positively with linoleate oxidation confirming in vivo the substrate/product relationship demonstrated in vitro, and negatively with TEE adjusted for fat-free mass, suggesting higher oxidative stress associated with increased torpor expression. This suggests a seasonal-dependant, cost-benefit trade-off between maximizing torpor propensity and minimizing oxidative stress that is associated with a shift toward sparing of dietary polyunsaturated fatty acids that is dependent upon the expression of a winter phenotype.

Mammary cell turnover and expression of lipogenic genes in response to silage induced CLA and diet energy density in lactating cows

The objective of this experiment was to investigate possible effects of silage induced differences in milk conjugated linoleic acids (CLA) and diet energy density on cell turnover and production capacity in the mammary gland. Cows were given high levels of canola fat and fed either grass or maize silage at either a high or a low diet energy density. Mammary biopsies were obtained and evaluated for cell turnover and gene expression. Diet energy density did not affect CLA concentration in milk fat and cell turnover. Feeding maize silage increased milk fat concentrations of cis9, trans11-CLA and trans10, cis12-CLA compared to grass silage. Cell proliferation tended to be greater in cows fed with maize compared to grass silage, indicating no negative effects of CLA on cell number. Feeding high energy density diets and maize silage diets tended to lower abundances of mammary lipogenic gene mRNAs presumable due to the effect of trans10, cis12-CLA.

Linoleate-Rich High-Fat Diet Decreases Mortality in Hypertensive Heart Failure Rats Compared With Lard and Low-Fat Diets

Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality. Both high-fat diets attenuated cardiac hypertrophy, left ventricular chamber dilation, and systolic dysfunction observed in rats consuming the high-carbohydrate diet. However, the lard diet significantly hastened heart failure mortality compared with the high-carbohydrate diet, whereas the linoleate diet significantly delayed mortality. Both high-fat diets elicited changes in the myocardial fatty acid profile, but neither had any effect on thromboxane excretion or blood pressure. The prosurvival effect of the linoleate diet was associated with a greater myocardial content and linoleate-enrichment of cardiolipin, an essential mitochondrial phospholipid known to be deficient in the failing heart. This study demonstrates that, despite having favorable effects on cardiac morphology and function in hypertension, a high-fat diet may accelerate or attenuate mortality in advanced hypertensive heart disease depending on its fatty acid composition. The precise mechanisms responsible for the divergent effects of the lard and linoleate-enriched diets merit further investigation but may involve diet-induced changes in the content and/or composition of cardiolipin in the heart.

Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer

Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content.

An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development?

A positive energy balance (energy intake>energy expenditure), in which total fat intake plays an important role, is commonly regarded as a major factor contributing to obesity. Adipose tissue development, i.e. both size (hypertrophy) and number (hyperplasia), is stimulated by high dietary fat intake during early postnatal development, a susceptibility that now appears to continue well into adulthood. Recent human and animal studies suggest that by altering rates of adipocyte differentiation and proliferation, differences in the composition of dietary fat may also contribute to adipose tissue development. At least in rodent models, the relative intake of n-6 to n-3 PUFA is clearly emerging as a new factor in this development. In these models, higher linoleate intake raises tissue arachidonic acid, which increases prostacyclin production and, in turn, stimulates signalling pathways implicated in adipogenesis. Signalling pathways stimulated by arachidonic acid probably include phospholipase and/or cyclo-oxygenase activation and may be linked as much to relatively low intake of n-3 PUFA as to excessive dietary linoleate. One factor potentially contributing to oversight about the apparent role of dietary n-6 PUFA (especially excess dietary linoleate) in adipose tissue development is the historical overestimation of linoleate requirements and the enthusiasm for higher intake of 'essential fatty acids'. More research is needed to address whether disequilibration of dietary PUFA intake contributes to the risk of obesity in humans.

Whole body distribution of deuterated linoleic and α-linolenic acids and their metabolites in the rat

Little is known about the uptake or metabolism of essential fatty acids (EFAs) in various mammalian organs. Thus, the distribution of deuterated alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) and their metabolites was studied using a stable isotope tracer technique. Rats were orally administered a single dose of a mixture (20 mg each) of ethyl D5-18:3n-3 and D5-18:2n-6, and 25 tissues per animal were analyzed for D5-labeled PUFAs at 4, 8, 24, 96, 168, 240, 360, and 600 h after dosing. Plasma, stomach, and spleen contained the highest concentrations of labeled precursors at the earliest time points, whereas other internal organs and red blood cells reached their maximal concentrations at 8 h. The time-course data were consistent with liver metabolism of EFAs, but local metabolism in other tissues could not be ruled out. Brain, spinal cord, heart, testis, and eye accumulated docosahexaenoic acid with time, whereas skin accumulated mainly 20:4n-6. On average, approximately 16-18% of the D5-18:3n-3 and D5-18:2n-6 initial dosage was eventually accumulated in tissues, principally in adipose, skin, and muscle. Approximately 6.0% of D5-18:3n-3 and 2.6% of D5-18:2n-6 were elongated/desaturated and stored, mainly in muscle, adipose, and the carcass. The remaining 78% of both precursors was apparently catabolized or excreted.

Fatty acid composition of plasma, medial basal hypothalamus, and uterine tissue in primiparous beef cows fed high-linoleate safflower seeds1

The experimental objectives were to evaluate the influence of supplemental high-linoleate safflower seeds on fatty acid concentrations in plasma, medial basal hypothalamus, uterine tissues, and serum 13,14-dihydro-15-keto PGF(2)alpha metabolite (PGFM) in primiparous beef cows during early lactation. Beginning 1 d postpartum, 18 primiparous, crossbred beef cows (411 +/- 24.3 kg of BW) were fed foxtail millet hay at 1.68% of BW (DM basis) and either a low-fat supplement (control: 63.7% cracked corn; 33.4% safflower seed meal; and 2.9% liquid molasses; DM basis) at 0.35% of BW (n = 9) or a supplement (linoleate) containing 95.3% cracked high-linoleate (79% 18:2n-6) safflower seeds and 4.7% liquid molasses (DM basis) at 0.23% of BW (n = 9). Diets were formulated to be isonitrogenous and isocaloric. The linoleate diet contained 5.4% of DMI as fat vs. 1.2% for control. Beginning 1 d postpartum, cattle were bled every 3 d for collection of serum and plasma. Cattle were slaughtered at 37 +/- 3 d postpartum for collection of the medial basal hypothalamus, myometrium, endometrium, caruncular tissue, intercaruncular tissue, and oviduct. Feeding linoleate increased (P = 0.001) plasma concentrations of 18:2n-6, 18:2cis-9 trans-11 and total unsaturated fatty acids; however, 18:1trans-11 did not differ (P = 0.19) between treatments. Concentrations of 20:5n-3 in the medial basal hypothalamus tended (P = 0.10) to be greater for cattle fed linoleate. Concentrations of fatty acids in the oviduct were greater (P < 0.05) than in other uterine tissues. Cows fed linoleate had greater (P = 0.05) concentrations of 18:3n-3 in the endometrium and less (P = 0.06) 18:2cis-9 trans-11 in the myometrium than cows fed the control. Supplemental fat increased (dietary treatment x day postpartum, P = 0.01) concentrations of PGFM in serum more in linoleate than control cows from d 3 to 9 postpartum. Lipid supplementation early in the postpartum period altered the fatty acid composition of medial basal hypothalamus, uterine tissue, and serum concentrations of PGFM. The most novel observation was that the oviduct appeared to be the most sensitive tissue to additional dietary linoleic acid, which could potentially influence fertility.

Influence of lipid class and fatty acid deficiency on survival, growth, and fatty acid composition in rainbow trout juveniles

Triplicate groups of rainbow trout (182 ± 51 mg) were fed four experimental casein–gelatin based diets containing different fatty acid levels for 8 weeks. Diet 1, containing only the oleic acid methyl ester (18:1 n − 9), was used as an essential fatty acids deficient diet. Diet 2, supplemented with olive and linseed oils was designed to provide moderate amount of linoleic (18:2 n − 6) and linolenic (18:3 n − 3) acids in the form of triglycerides. Diet 3 contained cod liver oil and provided highly unsaturated fatty acids (HUFA) as well as their precursors. Diet 4, supplemented with soy-refined lecithin, contained high levels of 18:2 n − 6 in the form of phospholipids. At the end of the experiment, the growth of fish fed the lecithin supplemented diet was significantly higher (17 fold increase) than that of the other groups (6–14 fold increase). Survival was significantly lower in fish fed the diet 1 in comparison to fish fed the other experimental diets (57.8% vs. 84.4–86.7%). Fish fed diets 1 and 4 contained significantly less total and neutral lipids in the whole body than fish fed diets 2 and 3. Whole body fatty acid profiles from both neutral and phospholipid fractions closely reflected dietary fatty acid composition. Fish fed linoleate containing phospholipids preferentially deposited this fatty acid in neutral lipids (33.0 ± 1.6%) in comparison to body phospholipids deposition (21.2 ± 1.0%). An increase of dietary linoleate also resulted in a significantly higher percentage of arachidonate (20:4 n − 6) in fish body phospholipids. In conclusion, selective accumulation of 18, 20, and 22 polyunsaturated fatty acids in body of juvenile rainbow trout is the function of fatty acid origin, e.g., lipid class, which has been very little studied in this species.