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At least 1,369 records · Page 76Linked to original sources
PubMed2005

New class of linoleic acid metabolites biosynthesized by corn and rice lipoxygenases: suppression of proinflammatory mediator expression via attenuation of MAPK- and Akt-, but not PPARgamma-, dependent pathways in stimulated macrophages.

In response to endogenous and exogenous stimuli, macrophages are activated to produce a cocktail of proinflammatory and anti-apoptotic mediators, thereby participating in the processes of inflammation-associated oncogenesis. Cereals, including corn and rice, have biological potentials to synthesize self-protective chemicals in order to repel the invasion of microorganisms and insects. We examined the suppressive effects of several fatty acids, including a new class of lipoxygenase metabolites of linoleic acid (LA) found in cereals, namely (+/-)-9-hydroxy-trans,cis-10,12-octadecadienoic acid (9-HOA from rice), (+/-)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA from corn), and (+/-)-10-oxo-trans-11-octadecen-13-olide (10-ODO from corn), on lipopolysaccharide (LPS)-induced mRNA expression of proinflammatory mediators in RAW264.7 murine macrophages. Each metabolite exhibited a suppressive activity toward nitrite production than LA, octadeca-9Z,11E-dienoic acid (a conjugated LA), and 13S-hydroxyoctadeca-9Z,11E-dienoic acid. LPS-up-regulated mRNA expression of inducible nitric oxide synthase, cyclooxygenase (COX)-2, interleukin-6, and toll-like receptor-2, -4, and -9 was also markedly attenuated without affecting the expression levels of several constitutive genes, including COX-1, as detected by reverse transcription-polymerase chain reactions. In addition, Western blot and luciferase reporter assay results showed that 13-HOA suppressed the phosphorylation of mitogen-activated protein kinases (extracellular signal-regulated kinasel/2, c-Jun N-terminal kinasel/2, p38 mitogen-activated protein kinase), and Akt (Ser473), and also attenuated degradation of inhibitor kappaB, nuclear translocation of nuclear factor kappaB (NFkappaB), and the transcriptional activities of NFkappaB and activator protein-1, both of which have essential roles in the transcription of numerous proinflammatory and oncogenic genes. In contrast, 13-HOA did not serve as a ligand for peroxisome proliferator-activated receptor-gamma. Based on our findings, we propose that 13-HOA, a functionally novel LA-derivative, is a promising agent for anti-inflammatory and chemopreventive strategies with reasonable molecular mechanisms.

Active Transport, Cell Nucleus↗
PubMed1994

Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro.

The purpose of the study was to compare the effects of dietary linoleic acid (LA) intake on the growth and metastasis of MDA-MB-435 and MDA-MB-231 human breast cancer cells in nude mice, together with their invasive capacity and secretion of type IV collagenase (gelatinase) in vitro. Each tumor cell line (10(6) cells) was injected into a right-sided mammary fat pad in 60 mice with equal numbers (30 mice/group) assigned to isocaloric diets containing 23% (w/w) total fat and 2% or 12% (w/w) LA. The MDA-MB-435-cell mammary fat pad tumors became palpable earlier and initially they grew more rapidly, but by 6 weeks the MDA-MB-231-cell tumors exhibited an acceleration of growth which was enhanced by the high-LA diet. At necropsy, 12 weeks after the tumor cell injections, the mean weight [10.2 +/- 1.4 g(SEM)] of mammary fat pad MDA-MB-231 cell tumors in 12% LA-fed mice was significantly higher (6.7 +/- 1.4 g) than that of the mice fed 2% LA; also, it was higher than that of MDA-MB-435 cell tumors in the 12% LA-fed mice (3.6 +/- 0.1 g) or the 2% LA-fed mice (3.3 +/- 0.1 g) (each P < 0.001). Mice fed the 12% LA diet had a higher incidence of grossly visible MDA-MB-435 cell pulmonary metastatic nodules than those fed the 2% LA diet (67% versus 33%; P < 0.02), more metastatic lesions (5.7 +/- 1.6 versus 2.3 +/- 0.8; P < 0.05), and greater total volumes (62.0 +/- 25.9 versus 24.8 +/- 9.0 mm3; P < 0.02) per mouse. Of the MDA-MB-231 cell tumor-bearing mice, only 1 in the 12% LA dietary group and 2 in the 2% LA dietary group had macroscopic nodules but the incidence of microscopic metastases was 68 and 42%, respectively. The MDA-MB-231 cell line exhibited a relatively high capacity for invasion in vitro and constitutively high levels of both total type IV collagenolytic activity and M(r) 92,000 gelatinase production which were unaffected by LA. In contrast, MDA-MB-435 cells had approximately only one-sixth the invasive capacity and secreted a relatively low level of type IV collagenase and little of the M(r) 92,000 gelatinase; both invasion and enzyme production were stimulated by LA.

Animals↗
PubMed1989

Effects of dietary linoleic acid on mucosal adaptation after small bowel resection.

We have shown that dietary long-chain triglycerides and 16,16-dimethyl prostaglandin E2 enhance and aspirin impairs postresection mucosal adaptation in rats. The present studies examined the hypothesis that supplemental linoleic acid (LA) above the minimum requirement may enhance postresection mucosal adaptation through altered prostaglandin (PG) synthesis. Forty male Sprague-Dawley rats (105 +/- 5 g) were fed purified diet containing either 5% LA or 4% palmitic acid and 1% LA. After 2 weeks, 12 rats from each dietary group underwent 70% proximal jejunoileal resection and the remainder were sham-operated. Dietary regimens were continued for an additional 13 days. Mucosal fatty acid analysis of 1% LA group revealed a ratio of 20:3 n-9/20:4 n-6 lower than 0.2, indicating normal essential fatty acid status. Mucosal protein per centimeter bowel was higher in the 5% LA group compared to the 1% group, but mucosal DNA, maltase, and ex vivo PG synthesis were not affected. These results indicate that LA stimulates postresection mucosal hypertrophy, which does not appear to be related to PG synthesis.

Adaptation, Physiological↗
PubMed2002

Effect of extruded full-fat soybeans on conjugated linoleic acid content of intramuscular, intermuscular, and subcutaneous fat in beef steers.

Crossbred Angus steers (n = 30) were used to determine whether the conjugated linoleic acid (CLA) content of beef fat could be increased by feeding varying levels of extruded full-fat soybeans as a source of polyunsaturated fatty acids for rumen biohydrogenation. Diets were as follows: 1) control, 2) 12.7% extruded full-fat soybeans (LESB), and 3) 25.6% extruded full-fat soybeans (HE SB). Steers were individually housed and fed the diets for 111 d during the finishing period. Over the experimental period, treatment groups were similar in ADG (1.7 +/- 0.1 kg/d) and had a similar slaughter weight (603 +/- 11.6 kg). Dressing percentage averaged 61.6% and carcass composition averaged 14.3% protein, 30.9% lipid, and 54.8% water. At slaughter, the intramuscular, intermuscular, and subcutaneous fat depots were sampled from the rib longissimus, eye of round, and chuck tender muscles. Across all fat depots, the CLA content differed (P < 0.05), averaging 6.6, 6.7, and 7.7 mg/g of fatty acids for the control, LESB, and HESB diets, respectively. There were significant differences in CLA content between fat depots within a cut, but differences were relatively small and the hierarchy in fat depots was not consistent among cuts. The cis-9, trans-11 isomer was the predominant CLA isomer and its content in fat was related to trans-11 C18:1 content (r = 0.53; P < 0.001). There was substantial individual variation in CLA content and this varied from 2.6 to 17.0 mg/g fatty acids across all treatments and fat depots. Overall, results demonstrated that including extruded full-fat soybeans in the diet of finishing steers increased the CLA content of beef fat. Differences were relatively small and the relationship of this to rumen fermentation and endogenous synthesis of CLA is considered.

Adipose Tissue↗
PubMed2003

A semi-quantitative RT-PCR method to measure the in vivo effect of dietary conjugated linoleic acid on porcine muscle PPAR gene expression.

Conjugated linoleic acid (CLA) can activate (in vitro) the nuclear transcription factors known as the peroxisome proliferators activated receptors (PPAR). CLA was fed at 11 g CLA/kg of feed for 45d to castrated male pigs (barrows) to better understand long term effects of PPAR activation in vivo. The barrows fed CLA had lean muscle increased by 3.5% and overall fat reduced by 9.2% but intramuscular fat (IMF %) was increased by 14% (P < 0.05). To measure the effect of long term feeding of CLA on porcine muscle gene expression, a semi-quantitative RT-PCR method was developed using cDNA normalized against the housekeeping genes cyclophilin and beta-actin. This method does not require radioactivity or expensive PCR instruments with real-time fluorescent detection. PPARgamma and the PPAR responsive gene AFABP but not PPARalpha were significantly increased (P < 0.05) in the CLA fed pig's muscle. PPARalpha and PPARgamma were also quantitatively tested for large differences in gene expression by western blot analysis but no significant difference was detected at this level. Although large differences in gene expression of the PPAR transcriptional factors could not be confirmed by western blotting techniques. The increased expression of AFABP gene, which is responsive to PPAR transcriptional factors, confirmed that dietary CLA can induce a detectable increase in basal PPAR transcriptional activity in the live animal.

Journal Article↗
PubMed1976

Kinetic analysis of the action of soybean lipoxygenase on linoleic acid.

The time course of the soybean lipoxygenase-catalyzed oxygenation of linoleic acid has been analyzed using a kinetic scheme based on two binding sites, compulsory product activation and competitive inhibition by substrate and by product. The dissociation constant (Kp) of the product from the free enzyme is much smaller than 10(-5) M, the dissociation constant of the substrate from the enzyme-substrate-product complex (Kps) has a value of (7.7 +/- 0.3) x 10(-6) M, and the competitive inhibitors constant of the product (Kpp) is equal to (2.9 +/- 0.3) x 10(-5) M Reduction of the hydroperoxide product to a hydroxy acid by sodium borohydride does not alter the product activation kinetics. From the study of the time course of the reaction, no evidence was found for the irreversible inactivation of the enzyme.

Kinetics↗
PubMed1982

Oral lecithin and linoleic acid in Friedreich's ataxia: I. Design of the study, material and methods.

A clinical and biochemical evaluation of twenty-two patients with Friedreich's Ataxia and ten normal controls was undertaken in 1980 to assess the effect of lecithin and linoleic acid supplements on the course of the disease. The trial consisted of two consecutive six months periods on either supplements in a double-blind crossover fashion. Clinical appraisal was performed with regards to the following parameters: joints mobility, muscle strength, equilibrium, coordination, motor accuracy, speech and numerous day to day activities. Blood samples were obtained at the beginning and in the course of the trial for enzymatic determinations. This paper describes the methodology of the study.

Administration, Oral↗
PubMed2006

The body fat-lowering effect of conjugated linoleic acid: a comparison between animal and human studies.

Different reasons which justify differences between rodents and humans in body fat reduction produced by conjugated linoleic acid (CLA) could be proposed. The doses used in humans are lower than those used in rodents. Human experiments have been performed with CLA isomer mixtures instead of isolated isomers. The variable dilution of t-10, c-12, the active isomer, among different preparations might explain the reduced responsiveness in humans. Diet composition may modulate CLA effects on body fat accumulation. As far as human studies are concerned, a specific dietary pattern has not been established. As a result differences among studies and also among subjects in the same study are likely. In rodents, the effects of CLA vary with genotype, suggesting that genetic predisposition to fat accumulation can play an important role in the effectiveness of CLA. Human volunteers with different body mass index have participated in the published studies and even in the same experiment. So, differences in lipid metabolism among subjects could help to explain the discrepancies observed in the literature. Age and maturity may also be crucial. Experiments using rodents have been conducted with growing animals and there is little evidence of CLA effectiveness in adult animals. By contrast, human studies have been performed with adults. Inhibition of lipogenesis in white adipose tissue is one of the mechanisms which have been proposed to explain the body-fat lowering effect of CLA, but lipogenesis in this tissue is very low in humans. Another mechanism suggested is increased fatty acid oxidation in the liver associated with peroxisome proliferation, but humans are relatively insensitive to this effect.

Adipose Tissue↗
PubMed2000

Isomers of conjugated linoleic acid (CLA) are incorporated into egg yolk lipids by CLA-fed laying hens.

This study was designed to determine the amount of conjugated linoleic acid (CLA) incorporated into egg lipids after dietary CLA supplementation. Single Comb White Leghorn laying hens (n = 40; 28 wk old) were randomly assigned to four treatments of varying CLA levels (0, 0.01, 0.5 and 1 g CLA/kg diet). Eggs were collected daily for 36 d. Feed consumption and body weight were monitored. CLA content of egg yolk lipid was analyzed by gas-liquid chromatography. Birds fed 0.5 and 1.0 g CLA/kg feed had significantly more CLA in the egg yolk lipid vs. control and 0.01 g CLA/kg diet groups after 7 d (P < 0.0004). Incorporation of CLA into egg lipid was highest on d 24 and 36. CLA enrichment in egg lipid in the 1.0 g CLA/kg diet group was similar to that in ruminant animal food products, approximately 3 mg CLA/g fat.

Animal Feed↗
PubMed2003

Dietary conjugated linoleic acids as free fatty acids and triacylglycerols similarly affect body composition and energy balance in mice.

The objective of this study was to compare the effects of conjugated linoleic acid (CLA) as triacylglycerols (TAG) or free fatty acids (FFA) on body composition and energy balance in mice. We fed four groups of 5-wk-old Balb-C mice (n = 9) semipurified diets containing either CLA (0.5 g CLA/100 g of diet) or high oleic sunflower oil (HOSF) in the form of FFA or TAG for 42 d. Body composition was determined and the energy in the carcasses, excreta and food was measured in a bomb calorimeter. The amount of body fat was 4.72 +/- 0.95 g (17.9 +/- 2.8%) in the HOSF-FFA group, 2.36 +/- 0.29 g (9.4 +/- 1.0%) in the CLA-FFA mice (mean +/- SD, P < 0.05), 4.76 +/- 0.74 g (18.2 +/- 2.2%) in the HOSF-TAG group and 2.32 +/- 0.38 g (9.3 +/- 1.1%) in the CLA-TAG mice (P < 0.05). The percentage of energy intake that was stored in the body was 3.5 +/- 1.2% in the HOSF-FFA group, 0.6 +/- 0.3% in the CLA-FFA group (P < 0.05), 3.5 +/- 1.1% in the HOSF-TAG group and 0.5 +/- 0.4 in the CLA-TAG mice (P < 0.05). Conversely, the percentage of energy intake that was expended as heat was 89.4 +/- 1.2% in the HOSF-FFA group, 92.4 +/- 0.8% in the CLA-FFA mice (P < 0.05), 89.47 +/- 1.23% in the HOSF-TAG group and 92.2 +/- 0.4% in the CLA-TAG group (P < 0.05). Thus, CLA in the form of FFA or TAG had similar effects on body composition and energy balance.

Animals↗
PubMed1988

Inhibition of renin by plasma linoleic acid.

The authors have demonstrated previously that human plasma contains an inhibitor(s) of the enzymatic activity of renin. The purpose of this study is to identify the circulating renin inhibitor. Plasma initially was fractionated with preparative sephacryl S-300 chromatography. A fraction with low protein content inhibited the in vitro enzymatic activity of human renin by 76%. The inhibitory activity of this fraction was not altered by boiling and/or acidification. This fraction was applied to an affinity column, using purified mouse submaxillary renin as ligand. The inhibitor was recovered after elution with hypertonic NaCl. Linoleic acid, a previously identified renin inhibitor, was present in this fraction. The authors conclude that circulating linoleic acid inhibits renin. Conceivably, the overall activity of the renin-angiotensin-aldosterone cascade may be modified by alterations of plasma fatty acid concentrations.

Angiotensin I↗
PubMed1997

Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic action of eritadenine in rats.

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20:4n-6/18:2n-6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of delta 6 desaturase in liver microsomes; there was significant correlation between the delta 6-desaturase activity and the 20:4n-6/18:2n-6 ratio in the PC of liver microsomes (r = 0.989, P < 0.001) or plasma (r = 0.986, P < 0.001). Certain plasma PC molecular species, as represented by 16:0-18.2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.

Adenine↗
PubMed2005

Anti-estrogenic effects of conjugated linoleic acid through modulation of estrogen receptor phosphorylation.

We previously showed that conjugated linoleic acids (CLA) can inhibit transcriptional activation mediated by estrogen response elements (EREs) and that this activity can, at least in part, account for the reported anti-tumor effects of these compounds on breast cancer cells. Using estrogen receptor positive (ER+) MCF-7 cells, we now demonstrate that CLA inhibited both the transactivation of artificial reporter constructs driven by canonical EREs, and the expression of endogenous progesterone receptors, a gene which is transcriptionally regulated by estrogen through novel ER-binding sites. This inhibition was accompanied by downregulation of ER alpha expression and decreased ER alpha-ERE binding activity. These effects on ER alpha were not causally linked since transfection of an ER alpha expression plasmid in MCF-7 cells failed to antagonize CLA downregulation of ER alpha-ERE binding. Immunoprecipitation/Western blot studies revealed that CLA dose-dependently suppressed the degree of phosphorylation of ER alpha, a modification known to inhibit receptor-ERE interactions. As a mechanism that may account for this induced dephosphorylation of ER alpha in MCF-7, we found that CLA specifically stimulated protein phosphatase 2A (PP2A) activity. Experiments using the PP2A inhibitor okadaic acid (OA) showed that OA antagonized both the dephosphorylation effects of CLA on ER alpha and its inhibition of ER alpha-ERE binding. These results provide evidence that the anti-estrogenic activity of CLA is caused by inducing the dephosphorylation of ER alpha through stimulation of PP2A activity.

Breast Neoplasms↗