OBJECTIVETo study the effects of different dietary fatty acid on the expression of nuclear receptor genes in the breast cancer of rats.

METHODSFifty-day-old female Sprague-Dawley rats were fed on eight different diets containing following fatty acids: saturated fatty acid (SFA); monounsaturated fatty acid (MUFA); n-6 polyunsaturated fatty acid (PUFA); n-3 PUFA; 1:1 n-6/n-3; 5:1 n-6/n-3; 10:1 n-6/n-3; 1:2:1 S/M/P (n-6/n-3 at 1:1). The rats were given a single intraperitoneal injection of methyl-nitrosourea (MNU) at 50 mg/kg body weight to establish the rat model of mammary carcinogenesis, the ultrastructure changes of mammary gland cells in rats were observed by transmission electron microscope, the cell proliferation activity was detected by BrdU-labeled immunocytochemistry, and the expression of PPARbeta and PPARgamma mRNA were assayed by RT-PCR.

RESULTSThere was no breast cancer occurring in control groups and the MNU-treated n-3 PUFA group, and the ultrastructure and proliferation activity of mammary gland cells in these groups were normal. In contrast, there appeared obvious marker of adenocarcinomas in mammary gland cells of MNU-induced breast cancer, and a high cell proliferation activity was found in tumor growth-enhancing groups (SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and S/M/P, 21% - 22% of BrdU-labeled cells), while a low cell proliferation activity was detected in rats fed with 1:1 n-6/n-3 diet (13% of BrdU-labeled cells, P < 0.05). Moreover, peroxisome proliferator-activated receptors (PPARs), as important nuclear receptor genes of relating lipid metabolism, the expressions of PPARbeta and PPARgamma mRNA were significantly up-regulated in mammary adipose tissues of MNU-induced breast cancer as compared with the control groups, but the expression levels of peroxisome proliferator-activated receptors (PPARs) in rats fed with 1:1 n-6/n-3 group were lowest (P < 0.05).

CONCLUSIONThe different dietary fatty acid compositions should diversely adjust the expression of PPARs gene in rats, which maybe have an important role in affecting incidence of breast cancer.

Animals ; Fatty Acids ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Mammary Neoplasms, Experimental ; genetics ; PPAR gamma ; genetics ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of n-3 polyunsaturated fatty acids(n-3PUFA) on human colorectal cancer cell line HT-29 and associated mechanism.

METHODSThe effects of docosahexaenoic acid (DHA) on the proliferation and apoptosis on HT-29 human colorectal cancer cells were evaluated by MTT assay, cell morphology (Hoechst33258 dyeing), DNA gel electrophoresis, and flow cytometry. The content of n-6PUFA and n-3PUFA of the treated cells and the ratio of n-6/n-3PUFA were analyzed by chromatography.

RESULTSDHA effectively inhibited HT-29 cell proliferation in a dose- and time-dependent manner. The proliferative inhibition rates of HT-29 cells treated with 10, 20, 40, and 80 mg/L DHA for 24 hours were 16.8%, 24.7%, 50.0%, and 60.1%, respectively, while the inhibition rates were 50.0%, 69.9%, and 77.0% respectively when HT-29 cells were treated with 40 mg/L DHA for 24, 48, and 72 hours. The typical apoptotic morphologic changes of HT-29 cells could be observed, including chromatin margination, nuclear condensation and apoptotic bodies. Gel electrophoresis of DNA degradation displayed typical DNA ladder fragments. HT-29 cells treated with DHA were arrested in G1 phase and the proportion of HT-29 cells in Gl phase increased compared with that of the control group (72.1% vs. 51.3%) while the proportion of the cells in S phase decreased significantly (19.9% vs. 38.9%). The content of n-6PUFA decreased, n-3PUFA content increased and the ratio of n-6/n-3PUFA lowered significantly in colorectal cancer cells treated with DHA (P<0.01).

CONCLUSIONSn-3PUFA can inhibit the growth of human colorectal cancer cells via inhibition of the proliferation and induction of apoptosis. These effects may be associated with decrease in n-6/n-3PUFA ratio.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; pathology ; Fatty Acids, Omega-3 ; pharmacology ; HT29 Cells ; Humans

OBJECTIVETo investigate the effect of n-3 polyunsaturated fatty acids (n-3PUFAs) on gut microbiota and endotoxin levels in portal vein of rats fed with a high-fat diet (HFD).

METHODSThirty-six male Sprague-Dawley rats were randomly divided into four groups and fed with normal control diet (CD), HFD, CD supplemented with n-3PUFAs, and HFD supplemented with n-3PUFAs, respectively. Fresh fecal samples were collected to analyze the gut microbiota 10 weeks after feeding. DNA was exacted from the fresh fecal samples. Quantitative PCR was used to detect the composition of the gut microbiota. The endotoxin levels were detected through modified azo chromogenic substrate limulus amebocyte lysate assay.

RESULTSThe differences in body weight before breeding in each group were not statistically significant among these four groups (P=0.613). The increase in the body weight was significantly larger in the HFD group than in the CD group (P=0.0002), CD+n-3PUFAs group (P=0.0001), and HFD+n-3PUFAs group (P=0.022). There were significantly more firmicutes (P=0.002) and enterobacteriales (P=0.022) and significantly less bacteroidetes (P=0.026) and bifidobactera (P=0.034) in the gut of rats from HFD group than those from the CD group. There were significantly more bacteroidetes in the fecal samples of the rats from the CD+n-3PUFAs group compared to those from the CD group (P=0.043). There were significantly more firmicutes (P=0.044)and enterobacteriales (P=0.012) and less bacteroidetes (P=0.042) in the fecal samples of the rats from HFD group compared to those from the HFD+n-3PUFAs group. The endotoxin in plasma form portal vein of rats in HFD group were significantly higher than in CD group (P=0.007) and HFD+n-3PUFAs group (P=0.042) but showed no significant difference between CD+n-3PUFAs and CD group (P=0.210).

CONCLUSIONSHFD can increase body weight and change gut microbiota. Supplementation of n-3PUFAs can partially counteract such gut dysbiosis, lower endotoxin level in portal vein blood, and improve the body weight.

Animals ; Body Weight ; Diet, High-Fat ; adverse effects ; Endotoxins ; blood ; Fatty Acids, Omega-3 ; pharmacology ; Intestines ; microbiology ; Male ; Microbiota ; drug effects ; Portal Vein ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo review the relation between dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA) and non-communicable diseases.

METHODData were collected from scientific journals and conference publications, MEDLINE (1979 - 2002) and current content which included 68 prospective, cross-sectional, case control and dietary-intervention studies. Scientific paper selections were based on the association between omega-3 PUFA and non-communicable diseases.

RESULTSomega-3 PUFA has beneficial effects on increasing heart rate variability, decreasing the risk of stroke, reducing both systolic and diastolic blood pressure, insulin resistance and glucose metabolism. Long chain omega-3 PUFA has anti-cancer and anti-inflammatory activities. omega-3 PUFA has also been reported to have a beneficial effect on attention-deficit/hyperactivity disorder and schizophrenia, and may be effective in managing depression in adults.

CONCLUSIONSResults from epidemiological and dietary intervention studies have shown that omega-3 PUFA represent powerfully a class of bioactive compounds and that dietary intake of omega-3 PUFA plays a critical role in human health in relation to non-communicable diseases.

Diabetes Mellitus ; therapy ; Fatty Acids, Omega-3 ; administration & dosage ; pharmacology ; Humans ; Hypertension ; prevention & control ; Inflammation ; prevention & control ; Lipids ; blood ; Mental Disorders ; therapy ; Neoplasms ; prevention & control ; Thrombosis ; prevention & control

OBJECTIVETo investigate the effect of omega-3 polyunsaturated fatty acids(omega-3PUFAs) on the apoptosis of human gastric cancer cell line SGC-7901 and to explore the potential mechanisms.

METHODSCells were treated with eicosapentaenoic acid (20:5 omega-3,EPA) or docosahexaenoic acid (22:6 omega-3, DHA) at concentrations of 10, 20 and 40 microg/ml. Cell growth and apoptosis were analyzed with MTT assay, cell morphology, DNA electrophoresis and flow cytometry. Mitochondrial membrane potential ( triangle right psi mt) was measured by fluorescent probe rhodamine 123. The distribution of cytochrome C in mitochondria and cytosol was determined by enzyme-linked immunoadsorbent assay. The composition of mitochondrial membrane phospholipid(MMP)was examined by gas chromatography.

RESULTSBoth EPA and DHA markedly inhibited the SGC-7901 cell growth and induced apoptosis in a time- and dose-dependent manner. After incubation of the cells with 40 microg/ml EPA or DHA for 24 hours, the level of Deltapsimt siginificantly decreased (P<0.001), and cytochrome C largely released into cytosol from mitochondria. The proportions of EPA and DHA in MMP rapidly elevated while that of arachidonic acid sharply decreased.

CONCLUSIONSomega-3PUFAs inhibit the growth of gastric cancer cells through promoting apoptosis. Compositional and functional alterations in mitochondrial membrane may be an important initiator of apoptosis induced by omega-3PUFAs.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cytochromes c ; metabolism ; Fatty Acids, Omega-3 ; pharmacology ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; metabolism ; pathology ; Stomach Neoplasms ; metabolism

The relationship between omega-3 polyunsaturated fatty acids (PUFAs) and violent-aggressive behavior has been payed attention since 1980s. Their correlation was explored by many epidemiological investigations, and the effect of PUFAs on prevention or reduction of violent-aggressive behavior in different groups were also affirmed by some intervention studies. This article summarized the previous studies and reviewed the history of epidemiological or intervention studies on PUFAs and its relationship with violent-aggressive behavior. It also presented the possible influencing factors in these studies and possible mechanisms.
Aggression ; Animals ; Dietary Fats, Unsaturated/pharmacology* ; Dietary Supplements ; Docosahexaenoic Acids/pharmacology* ; Eicosapentaenoic Acid/pharmacology* ; Fatty Acids, Omega-3/pharmacology* ; Fatty Acids, Omega-6/pharmacology* ; Fishes ; Folic Acid/metabolism* ; Humans ; Hydroxyindoleacetic Acid/metabolism* ; Norepinephrine/metabolism* ; Risk Factors ; Serotonin/metabolism* ; Violence/prevention & control*

OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) &omega;-3 and &omega;-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

METHODSThe effects of &omega;-3, &omega;-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of &omega;-3, &omega;-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without &omega;-3, &omega;-6, PGE2 and PGE3 were designed as the control.

RESULTSWith the increased concentration of &omega;-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of &omega;-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by &omega;-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of &omega;-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by &omega;-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, &omega;-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, &omega;-6 could increase angiogenesis of gastric cancer cells(P<0.01), but &omega;-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, &omega;-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but &omega;-6 had no effect on angiogenesis.

CONCLUSIONSThe PUFA &omega;-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the &omega;-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.

Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology

OBJECTIVE: To explore the correlation between the eicosapentaenoic acid(EPA), docosahexaenoic acid (DHA) and the aggressive behavior in mice. METHODS: Seventy-two male Kunming mice were divided into control group, fish oil group, simvastatin group and aggressive reference group randomly. The control group, fish oil group and simvastatin group were given normal saline, fish oil and simvastatin by irrigation respectively for 3 months consecutively, each mouse was raised isolatedly. The latent period of assault, the frequencies of tail swing and assault, and the cumulative time of assault were recorded at the beginning and the end of the intervention. Finally, the EPA and DHA in brain were analyzed by gas chromatography-mass spectrometry (GC-MS). The aggressive reference group was raised without intervention and was evaluated as aggressive reference only. RESULTS: (1) Before intervention, the latent period of assault, the frequencies of tail swing, the frequencies of assault, and the cumulative time of assault were not significantly different from each other group. After intervention, the differences were significant (P<0.05). (2) After the intervention, the content of EPA and DHA in mice brain was the most in the fish oil group, and the least in the simvastatin group. (3) The content of EPA was negatively related with the four indexes (P<0.05) before and after the intervention. The content of DHA was negatively related with the frequencies of tail swing and assault (P<0.05). CONCLUSION There is a correlation between the EPA, DHA and aggressive behavior in mice under stress.
Aggression/physiology* ; Animals ; Behavior, Animal/physiology* ; Brain/metabolism* ; Docosahexaenoic Acids/metabolism* ; Eicosapentaenoic Acid/metabolism* ; Fatty Acids, Omega-3/metabolism* ; Fish Oils/pharmacology* ; Gas Chromatography-Mass Spectrometry ; Male ; Mice ; Random Allocation ; Simvastatin/pharmacology*

INTRODUCTIONThis study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus.

METHODSA total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured.

RESULTSArylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors.

CONCLUSIONVitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

Animals ; Aryldialkylphosphatase ; metabolism ; Ascorbic Acid ; pharmacology ; Carboxylic Ester Hydrolases ; metabolism ; Diabetes Mellitus, Experimental ; diet therapy ; metabolism ; Dietary Supplements ; Fatty Acids, Omega-3 ; pharmacology ; Liver ; enzymology ; Male ; Myocardium ; enzymology ; Rats ; Rats, Sprague-Dawley ; Vitamin A ; pharmacology ; Vitamins ; pharmacology

OBJECTIVETo investigate the impact of intestinal lymphatic vessels ligation and different enteral nutrition support during ischemia/reperfusion on intestinal permeability, systemic inflammatory response and pulmonary dysfunction in a rat model.

METHODSSeventy-two Sprague-Dawley male rats were randomized into normal diet group, regular enteral nutrition group, glutamine-enriched group, 0-3 polyunsaturated fatty acids (wo-3PUFA) group, and sham control after gastrostomy. All the enteral nutrition group were isocaloric (1046 kJ kg-' d-1) and isonitrogenous (1.8 g N kg-' d-'). After enteral nutrition for 7 days, the rats were subjected to intestinal ischemia for 60 min, or ischemia plus mesenteric lymph duct ligation except for the sham group followed by 3 days of nutrition (72 h). Intestinal permeability (lactose/mannitol ratio in the urine, L/M) was determined on the 5th, 7th and 9th day after gastrostomy. The levels of serum diamine oxidase, endotoxin, cytokines, ALT and AST were detected at the 11th day after gastrostomy. Mucosal thickness was measured using small intestine and villusheight. Myeloperoxidase (MPO), nitric oxide (NO), NO synthase, and apoptotic index were detected in lung tissue.

RESULTSIschemia for 60 min could cause intestinal injury. Intestinal permeability(L/M)was increased significantly in every group on the first day after ischemia (P<0.05). However, L/M decreased significantly 3 days after ischemia (P<0.05). The groups with Glu and o-3PUFA-enriched nutrition almost restored to normal level (P>0.05). The level of L/M in lymphatic ligation group was significantly lower than non-ligation group (P<0.05). The levels of endotoxin and cytokine were reduced, mucosal thickness and villous height were significantly higher (P<0.05) in the groups of Glu and o-3PUFA-enriched nutrition compared with enteral nutrition and normal diet groups during intestinal ischemia-reperfusion injury. MPO, NO, NOS and the apoptosis index of lung tissue decreased in the groups of Glu and o-3PUFA-enriched as well as after lymph duct ligation (P<0.05).

CONCLUSIONSThe distant tissue-lung damage and systemic inflammation caused by intestinal ischemia-reperfusion injury may be related to some factors in the intestinal lymph. Blocking the gut-lymph pathway and/or adding Glu and o-3PUFA in enteral nutrition may reduce intestinal permeability and endotoxin, increase mucosal thickness, attenuate the systemic inflammatory reaction, and prevent lung injury

Animals ; Apoptosis ; drug effects ; Disease Models, Animal ; Enteral Nutrition ; methods ; Fatty Acids, Omega-3 ; pharmacology ; Glutamine ; pharmacology ; Intestines ; blood supply ; physiopathology ; Ligation ; Lung ; pathology ; Lymphatic Vessels ; Male ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology ; physiopathology ; therapy