Dietary Linoleic Acid Research Articles

Conjugated linoleic acid improves glucose utilization in the soleus muscle of rats fed linoleic acid–enriched and linoleic acid–deprived diets

The effect that conjugated linoleic acid (CLA) has on glucose metabolism in experimental animals depends on nutritional conditions. Therefore, we hypothesized that CLA improves glucose utilization and insulin sensitivity in rats fed different levels of dietary linoleic acid (LA). We investigated the effect of CLA on the uptake, incorporation, and oxidation of glucose and glycogen synthesis in the soleus muscle of rats who were fed either LA-enriched (+LA) or LA-deprived (−LA) diets, under basal conditions and in the absence or presence of insulin and/or palmitate. For 60 days, male Wistar rats were fed 1 of 4 diets consisting of +LA, −LA, or +LA and −LA supplemented with CLA. Nutritional parameters and soleus glucose metabolism were evaluated. Under basal conditions, CLA enhanced soleus glucose oxidation, whereas increased glucose uptake and incorporation were observed in the −LA + CLA group. Conjugated linoleic acid–supplemented rats presented a lower response to insulin on glucose metabolism compared with non–CLA-supplemented rats. Palmitate partially inhibited the effect of insulin on the uptake and incorporation of glucose in the +LA and –LA groups but not in the +LA + CLA or −LA + CLA groups. Dietary CLA increased glucose utilization under basal conditions and prevented the palmitate-induced inhibition of glucose uptake and incorporation that is stimulated by insulin. The beneficial effects of CLA were better in LA-deprived rats. Conjugated linoleic acid may also have negative effects, such as lowering the insulin response capacity. These results demonstrate the complexities of the interactions between CLA, palmitate, and/or insulin to differentially modify muscle glucose utilization and show that the magnitude of the response is related to the dietary LA levels.

CYP341B14: A cytochrome P450 involved in the specific epoxidation of pheromone precursors in the fall webworm Hyphantria cunea

Two of the four sex pheromone components in the fall webworm Hyphantria cunea (Lepidoptera: Arctiidae), cis-9,10-epoxy-(3Z,6Z)-3,6-henicosadiene and cis-9,10-epoxy-(3Z,6Z)-1,3,6-henicosatriene, possess an epoxy ring within their molecules. These compounds have been suggested to be biosynthesized from dietary linolenic acid via the following enzymatic reactions; chain elongation, terminal desaturation (in the case of the latter component), decarboxylation, and epoxidation. The last step of this biosynthesis, epoxidation, is known to occur specifically in the sex pheromone gland of females. We identified the enzyme involved in the epoxidation of pheromone precursors by focusing on cytochromes P450, which are known to catalyze the oxidation of various compounds. Three P450-like sequences (Hc_epo1, Hc_epo2, and Hc_epo3) were identified in the cDNA library prepared from the sex pheromone gland of H. cunea. Among these clones, only Hc_epo1 was specifically expressed in the pheromone gland. The full-length sequence of Hc_epo1 contained an ORF of 1527 bp, which encoded a protein of 509 amino acids with a predicted molecular weight of 57.9 kDa. The deduced Hc_epo1 amino acid sequence possessed the characteristics of P450. A phylogenetic analysis of the sequence indicated that Hc_epo1 belonged to the CYP341B clade in the CYP341 family. Therefore, it was named CYP341B14. A subsequent functional assay using Sf-9 cells transiently expressing CYP341B14 demonstrated that this P450 protein was able to specifically epoxidize a (Z)-double bond at the 9th position in the pheromone precursor, (3Z,6Z,9Z)-3,6,9-henicosatriene.

Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

Stearic acid (C18:0) is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil), or oleic acid (corn oil) enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1) compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death) and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2) and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies.

Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78-0.92; I(2)=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71-0.89; I(2)=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82-0.94). In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose-response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

Relationship between a Common Variant in the Fatty Acid Desaturase (FADS) Cluster and Eicosanoid Generation in Humans

Dramatic shifts in the Western diet have led to a marked increase in the dietary intake of the n-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA). Dietary LA can then be converted to arachidonic acid (ARA) utilizing three enzymatic steps. Two of these steps are encoded for by the fatty acid desaturase (FADS) cluster (chromosome 11, 11q12.2-q13) and certain genetic variants within the cluster are highly associated with ARA levels. However, no study to date has examined whether these variants further influence pro-inflammatory, cyclooxygenase and lipoxygenase eicosanoid products. This study examined the impact of a highly influential FADS SNP, rs174537 on leukotriene, HETE, prostaglandin, and thromboxane biosynthesis in stimulated whole blood. Thirty subjects were genotyped at rs174537 (GG, n = 11; GT, n = 13; TT, n = 6), a panel of fatty acids from whole serum was analyzed, and precursor-to-product PUFA ratios were calculated as a marker of the capacity of tissues (particularly the liver) to synthesize long chain PUFAs. Eicosanoids produced by stimulated human blood were measured by LC-MS/MS. We observed an association between rs174537 and the ratio of ARA/LA, leukotriene B4, and 5-HETE but no effect on levels of cyclooxygenase products. Our results suggest that variation at rs174537 not only impacts the synthesis of ARA but the overall capacity of whole blood to synthesize 5-lipoxygenase products; these genotype-related changes in eicosanoid levels could have important implications in a variety of inflammatory diseases.

Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation

Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.

Egg Size of Saudi Local Layers as Affected by Line of the Bird (Body Weight at Sexual Maturity) and Dietary Fat Level

Egg size is an important economic factor that determines the profitability of the producer. Most of the eggs produced by the local birds are small and do not command market price. Nutrition and Management may play an important role in altering the size of the egg. This study was conducted to evaluate the use of different weight groups at sexual maturity (line of the bird) and different levels of supplemental fat on performance and egg size of the Saudi local birds. To achieve that a 2 x 3 factorial arrangement was used on 120 local hens. These hens were assigned to 6 treatments namely 2 weight groups and 3 levels of added fat 0, 2 and 4% corn oil at the age of 22 weeks. Data obtained from week 22 to 28 were not included in the average performance of the birds due to the large number of missing data. Performance criteria and egg characteristics were used to test the hypothesis of the study. Result of the study showed a significant effect of linoleic acid (corn oil) on the average egg weight. There was a clear indication that as level of corn oil increased from 0 to 4%, size of the eggs increased accordingly. The effect of interaction between level of fat and line (weight) of the bird on egg weight was highly significant (p<0.001). Brown birds (medium in weight) responded better to the higher level of linoleic acid in the diet with 51 g of egg weight compared to the lower level of dietary linoleic acid and the control in the same group, 48.11 and 47.29 g, respectively and also to the treatments of the other group (black, small in weight). Egg production, egg mass and feed efficiency were highly affected by the two lines and the interaction with fat level favoring the 4% corn oil (when fed to the larger line (Brown birds). Effect of added fat corn oil (linoleic acid) on egg characteristics was significant (p<0.01) for yolk color and Haugh unit. Better Albumen quality was found with the higher level of fat (4% corn oil) but with less yellowish yolk color as measured by La-Rroche fan. In conclusion and based upon the results of this study, it is suggested that linoleic acid play an important role in maximizing the egg size of the local birds and adding 4% corn oil without jeopardizing the energy content of the ration may be a good way of improving the egg size of the Saudi local brown birds during the onset and first part of the laying year.

Dietary Intake and Weight Gain Among Adolescents on Depot Medroxyprogesterone Acetate

Study ObjectiveTo examine the relationship between dietary intake and weight gain among adolescent females initiating depot medroxyprogesterone acetate (DMPA). DesignProspective observational study. SettingTwo urban Adolescent Medicine clinics. Participants45 postmenarchal females, age 12 to 21, enrolled after self-selecting to initiate DMPA. InterventionParticipants received 150 mg DMPA intramuscularly every 12 weeks. Height, weight, and 24-hour dietary recall were collected at baseline, 3, 6, and 12 months. Main Outcome MeasureBody mass index (BMI) over time calculated as weight (kg)/height (m2). Associations between dietary variables and BMI were evaluated with repeated measures analysis of variance modeling. ResultsMean chronological and gynecologic ages were 16.2 ± 1.5 and 4.2 ± 1.8 years, respectively. Mean BMI increased from 23.7 ± 5.3 to 25.3 ± 5.7 over 12 months. Average dietary intake included: 1781.4 ± 554.1 total kilocalories, 228.5 g ± 69.8 carbohydrates, 71.0 g ± 27.3 fat, and 61.0 g ± 20.2 protein. These diet measures were not associated with BMI over time. Dietary fiber, magnesium, and linoleic acid were inversely associated with increased BMI over time (P < .05) ConclusionWe found no evidence that general measures of diet (energy, carbohydrates, fat, and protein), as assessed by 24-hour recall, were predictive of weight gain on DMPA. Several nutrients abundant in foods that benefit overall health were inversely associated with increased BMI over time, suggesting that diet quality, rather than quantity, is a more important predictor of DMPA-associated weight gain.

Differential response of Iberian and lean pig crossbreeds to dietary linoleic acid administration

We aimed to determine whether the response of linoleic acid (C18:2 n-6) tissue concentration to dietary C18:2 n-6 administration, in the finishing period, is done in a different way in Iberian pig compared with a lean genotype. Therefore, 48 pigs, 24 of a lean genotype (Large White × Great York) and 24 of a fat genotype (Iberian × Duroc) were offered three commercial diets, for each genetic type, in order to provide three levels of C18:2 n-6, but maintaining constant the concentration of saturated and linolenic fatty acids (FA) in each genotype. Samples from adipose tissue (subcutaneous backfat and intramuscular fat (IMF) from Longissimus dorsi muscle) were taken. Six pigs of each genotype (two per each C18:2 n-6 level) were slaughtered at the start of the trial to estimate initial fatty acids composition. The C18:2 n-6 proportions at slaughter were higher in the subcutaneous backfat outer layer than in subcutaneous backfat inner layer for both genetic types. In both backfat layers, as the dietary C18:2 n-6 increased, the C18:2 n-6 proportions also increased in both genotypes. In IMF, the concentration of C18:2 n-6 was also altered in lean genotype according to dietary treatment, but no response was observed in Iberian pigs. Linoleic acid concentrations was higher in lean pig genotypes than in the Iberian pig, both in subcutaneous and IMF throughout the whole range of dietary linoleic acid concentration used in this experiment. These results indicate the resistance of Iberian pig to modify the proportion of linoleic in their tissues, particularly in the IMF.

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.

Different dietary fatty acids are associated with blood lipids in healthy South African men and women: The PURE study

BackgroundPreliminary data from the baseline Prospective Urban Rural Epidemiology (PURE) study in South Africa indicated a higher prevalence of dyslipidemia than previous South African studies. The intake of specific individual dietary fatty acids may affect blood lipids differently than sub-groups of fat (i.e. polyunsaturated fatty acids). We investigated the dietary intake of different individual fatty acids and their associations with blood lipids, in relation to urbanization and gender. MethodsCross-sectional data analysis within the PURE baseline study of healthy subjects (n=1950, 35–70years) from rural and urban areas. Dietary data were collected and blood lipid analysis performed. ResultsIntake of individual fatty acids was significantly higher in urban than rural dwellers. However, the intake of n-3 PUFAs was below recommendations in all groups. Total cholesterol and LDL were higher in females than in males, with no rural‒urban differences. Intake of alpha-linolenic acid (ALA) was positively associated with total cholesterol (β=0.143) and triglycerides (β=0.256) in males. The risk for having elevated LDL also increased with increased intake of ALA (OR 1.49, 95% CI 1.04, 2.14) in males. In females, arachidonic acid and eicosapentaenoic acid (EPA) were positively associated with total cholesterol and arachidonic acid was also positively associated with LDL, whereas docosahexaenoic acid was negatively associated with total cholesterol and LDL. ConclusionsThese results suggest that specific individual dietary fatty acids may affect blood lipids in males differently than in females irrespective of rural or urban dwelling. The positive association between ALA and total cholesterol and triglycerides in males is a concern, because current advice aims to improve the dietary linoleic acid to ALA ratio by increasing ALA intake.

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition.

A dietary combination of sucrose and linoleic acid strongly contributes to the development of metabolic disorders in Zucker fatty rats. However, the underlying mechanisms of the metabolic disorders are poorly understood. We hypothesized that the metabolic disorders were triggered at a stage earlier than the 8 weeks we had previously reported. In this study, we investigated early molecular events induced by the sucrose and linoleic acid diet in Zucker fatty rats by comparison with other combinations of carbohydrate (sucrose or palatinose) and fat (linoleic acid or oleic acid). Skeletal muscle arachidonic acid levels were significantly increased in the sucrose and linoleic acid group compared to the other dietary groups at 4 weeks, while there were no obvious differences in the metabolic phenotype between the groups. Expression of genes related to arachidonic acid synthesis was induced in skeletal muscle but not in liver and adipose tissue in sucrose and linoleic acid group rats. In addition, the sucrose and linoleic acid group exhibited a rapid induction in endoplasmic reticulum stress and abnormal lipid metabolism in skeletal muscle. We concluded that the dietary combination of sucrose and linoleic acid primarily induces metabolic disorders in skeletal muscle through increases in arachidonic acid and endoplasmic reticulum stress, in advance of systemic metabolic disorders.

Dietary gamma-linolenic acid supports arachidonic acid accretion and associated Δ-5 desaturase activity in feline uterine but not ovarian tissues

Arachidonic acid (ARA) is essential in felines because conversion of dietary linoleic acid (LA) to ARA is rate-limited by low Δ6-desaturase. Dietary γ-linolenic acid (GLA) may serve as an ARA precursor by-passing this initial rate-limiting step. This possibility was investigated using twenty-six adult female domestic shorthair cats divided into three groups and fed on complete and balanced diets containing high GLA (GL), high LA (HL) or low LA (LL, control) diets, for 300d prior to ovariohysterectomy. Plasma was obtained 1-2d before surgery and uterine, ovarian and associated adipose tissues were reserved for lipid analysis. Fatty acid profiles of the plasma phospholipid (PL) fractions and adipose lipids were performed. In the GL group, plasma and uterine tissue PL were significantly enriched in GLA, di-homo GLA (DGLA) and ARA compared with control. However, ovarian and adipose tissue PL were only enriched in DGLA. Enrichment of uterine tissues with DGLA and ARA probably supplies the essential eicosanoid precursors for reproduction when GLA is fed consistently with an active Δ5-desaturase in uterus. By contrast, this enzyme appears less active in ovary because ARA was not higher compared with control. Earlier reports concluded that ARA was not necessary for fertilisation (an ovarian function), but required for successful pregnancy and reproduction (a uterine function). Adipose tissue DGLA may be a reservoir for ARA synthesis by other tissues upon mobilisation. Dietary GLA may meet feline ARA requirements in the absence of an animal-based preformed source of ARA.

Discovery of a disused desaturase gene from the pheromone gland of the moth Ascotis selenaria, which secretes an epoxyalkenyl sex pheromone

Female Ascotis selenaria (Geometridae) moths use 3,4-epoxy-(Z,Z)-6,9-nonadecadiene, which is synthesized from linolenic acid, as the main component of their sex pheromone. While the use of dietary linolenic or linoleic fatty acid derivatives as sex pheromone components has been observed in moth species belonging to a few families including Geometridae, the majority of moths use derivatives of a common saturated fatty acid, palmitic acid, as their sex pheromone components. We attempted to gain insight into the differentiation of pheromone biosynthetic pathways in geometrids by analyzing the desaturase genes expressed in the pheromone gland of A. selenaria. We demonstrated that a Δ11-desaturase-like gene (Asdesat1) was specifically expressed in the pheromone gland of A. selenaria in spite of the absence of a desaturation step in the pheromone biosynthetic pathway in this species. Further analysis revealed that the presumed transmembrane domains were degenerated in Asdesat1. Phylogenetic analysis demonstrated that Asdesat1 anciently diverged from the lineage of Δ11-desaturases, which are currently widely used in the biosynthesis of sex pheromones by moths. These results suggest that an ancestral Δ11-desaturase became dysfunctional in A. selenaria after a shift in pheromone biosynthetic pathways.

Adipose tissue fatty acid composition and colon cancer: a case–control study

An increased dietary intake of fat, particularly polyunsaturated fatty acids (PUFAs), has been related to an increased risk of breast, prostate and colon cancers. Patients with and without colon cancer were tested for differences in their fatty stores composition. The fatty acid levels were determined by gas-liquid chromatography in adipose tissue samples, subcutaneous and visceral, obtained intra-operatively from 52 colon cancer and 50 nonneoplastic abdominal disease patients. Statistical analysis was performed using one-way ANOVA, SNK test and Dunnet test. Differences in the composition of saturated, monounsaturatedand polyunsaturated fatty acids, in visceral and in subcutaneous samples of colon cancer and nonneoplastic patients, were assessed. The sum of saturated and monounsaturated fatty acids, respectively, in visceral and in subcutaneous samples, was higher in neoplastic patients (p<0.001). The sum of some n-6 polyunsaturated fatty acids (PUFAs), the dietary precursor linoleic acid (LA-18:2n-6), and their metabolites, gammalinolenic acid (GLA-18:3n-6)+dihomogammalinolenic acid (DGLA-20:3n-6)+arachidonic acid (AA-22:4n-6), was higher in subcutaneous fat of controls (p<0.05). The samples from these patients had a fatty acid composition, both subcutaneous and visceral, with a higher content of alphalinolenic acid (ALA-18:3n-3) and stearidonic acid (SDA-18:4n-3) compared to neoplastic patients (p<0.001). These had subcutaneous and visceral fat stores statistically higher in GLA, DGLA and AA (p<0.001). Colon cancer patients had subcutaneous adipose stores higher in ALA and LA than visceral sites (p<0.001). Fatty acids may be involved in colon carcinogenesis and there is a depot-specific impact on this process by visceral fat.

Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins

The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat isocaloric diets. Animal growth rates and mitochondrial respiratory parameters were essentially unaffected, but mass spectrometry-based mitochondrial lipidomics profiling revealed increased levels of cardiolipins (CLs), a family of phospholipids essential for mitochondrial structure and function, in rats fed saturated or trans fat-based diets with a high glycemic index. These mitochondria showed elevated monolysocardiolipins (a CL precursor/product of CL degradation), elevated ratio of trans-phosphocholine (PC) (18:1/18:1) to cis-PC (18:1/18:1) (a marker of thiyl radical stress), and decreased ubiquinone Q9; the latter two of which imply a low-grade mitochondrial redox abnormality. Extended analysis demonstrated: i) dietary fats and, to a lesser extent, carbohydrates induce changes in the relative abundance of specific CL species; ii) fatty acid (FA) incorporation into mature CLs undergoes both positive (>400-fold) and negative (2.5-fold) regulation; and iii) dietary lipid abundance and incorporation of FAs into both the CL pool and specific mature tetra-acyl CLs are inversely related, suggesting previously unobserved compensatory regulation. This study reveals previously unobserved complexity/regulation of the central lipid in mitochondrial metabolism.

Dietary Linoleic Acid Elevates the Endocannabinoids 2‐AG and Anandamide and Promotes Weight Gain in Mice Fed a Low Fat Diet

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA–PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.

N-3 essential fatty acids in Nile tilapia, Oreochromis niloticus: Quantification of optimum requirement of dietary linolenic acid in juvenile fish

To quantify the optimum requirement of dietary linolenic acid (18:3n-3, LNA) for Nile tilapia (Oreochromis niloticus), purified ethyl linolenate was added to the basal diet to provide the dietary LNA level of 0.00, 0.10, 0.32, 0.63, 0.98, 1.56 and 2.04% of dry weight, respectively. All diets contained similar amounts of 18:2n-6 (0.61% of dry weight) and 18:1n-9 from purified ethyl linoleate and oleate, respectively. Basal diet without LNA was considered as a control. After 2-week acclimation with a lipid-free diet, 4 replicate groups of 120 juvenile fish with initial body weight of 2.10g were fed with experimental diets in a recirculated fresh water rearing system for 10weeks. Feeding rate was 10% of body weight in the first 2weeks, 8% in the following 4weeks, and then gradually reduced to 5% in the next 4weeks. Fish were fed three times daily at 8:30, 12:00 and 17:00. The results showed that fish fed the diet with 0.63% of LNA had significantly higher weight gain (WG) and specific growth rate (SGR) than fish fed the control diet (P<0.05). Feed efficiency (FE) and protein deposition (PD) in fish fed diets with 0.63, 0.98, 1.56 and 2.04% of LNA were significantly higher than those of the control group (P<0.05). Fish muscle fatty acid composition reflected dietary fatty acids. Increasing dietary LNA levels resulted in increased contents of LNA and 22:6n-3, but decreased contents of 20:4n-6 and 20:5n-3. When WG and FE were subjected to broken-line regression analysis, the breakpoint was achieved at dietary LNA levels of 0.45 and 0.64% of dry weight, respectively. Based on those results, the recommended optimum requirement of dietary LNA for juvenile tilapia is 0.45–0.64% of dry weight.

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.