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At least 271 records · Page 15Linked to original sources
PubMed1999

Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells.

Epidemiologic and animal studies have linked pancreatic cancer growth with fat intake, especially unsaturated fats. Arachidonic acid release from membrane phospholipids is essential for tumor cell proliferation. Lipoxygenases (LOX) constitute one pathway for arachidonate metabolism, but their role in pancreatic cancer growth is unknown. The expression of 5-LOX and 12-LOX as well as their effects on cell proliferation was investigated in four human pancreatic cancer cell lines (PANC-1, MiaPaca2, Capan2, and ASPC-1). Expression of 5-LOX and 12-LOX mRNA was measured by nested RT-PCR. Effects of LOX inhibitors and specific LOX antisense oligonucleotides on pancreatic cancer cell proliferation were measured by (3)H-thymidine incorporation. Our results showed that (1) 5-LOX and 12-LOX were expressed in all pancreatic cancer cell lines tested, while they were not detectable in normal human pancreatic ductal cells; (2) both LOX inhibitors and LOX antisense markedly inhibited cell proliferation in a concentration-dependent and time-dependent manner; (3) the 5-LOX and 12-LOX metabolites 5-HETE and 12-HETE as well as arachidonic and linoleic acids directly stimulated pancreatic cancer cell proliferation; (4) LOX inhibitor-induced growth inhibition was reversed by 5-HETE and 12-HETE. The current studies indicate that both 5-LOX and 12-LOX expression is upregulated in human pancreatic cancer cells and LOX plays a critical role in pancreatic cancer cell proliferation. LOX inhibitors may be valuable for the treatment of pancreatic cancer.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1999

Lipoxygenase inhibition induced apoptosis, morphological changes, and carbonic anhydrase expression in human pancreatic cancer cells.

Epidemiologic and animal studies have linked pancreatic cancer growth with fat intake, especially unsaturated fats. Arachidonic acid release from membrane phospholipids is essential for tumor cell proliferation. Lipoxygenases (LOX) constitute one pathway for arachidonate metabolism. We previously reported that 5-LOX and 12-LOX are upregulated in human pancreatic cancer cells and that blockade of these enzymes abolishes pancreatic cancer cell growth. The present study was aimed at evaluating the effect of LOX inhibition on differentiation and apoptosis in pancreatic cancer cells in parallel with growth inhibition. Four human pancreatic cancer cell lines, PANC-1, MiaPaca2, Capan2, and HPAF, were used. Apoptosis was evaluated by three separate methods, including DNA propidium iodide staining, DNA fragmentation, and the TUNEL assay. Morphological changes and carbonic anhydrase activity were used to determine the effect of LOX inhibitors on differentiation. The general LOX inhibitor NDGA, the 5-LOX inhibitor Rev5901, and the 12-LOX inhibitor baicalein all induced apoptosis in all four pancreatic cancer cell lines, as confirmed by all three methods, suggesting that both the 5-LOX and 12-LOX pathways are important for survival of these cells. Furthermore, NDGA, Rev5901, or baicalein resulted in marked cellular morphological changes in parallel with increased intracellular carbonic anhydrase activity, indicating that LOX blockade induced a more differentiated phenotype in human pancreatic cancer cells. Together with our previous findings, this study suggests that perturbations of LOX activity affect pancreatic cancer cell proliferation and survival. Blockade of LOX enzymes may be valuable for the treatment of human pancreatic cancer.

Apoptosis↗
PubMedDate not supplied

Influence of dietary unsaturated and saturated fat on the plasma lipoproteins of Mongolian gerbils.

Lipid and apoprotein moieties of the plasma lipoproteins of Mongolian gerbils (Meriones unguiculatus) were compared in animals fed semipurified diets containing either coconut oil (COC) or safflower oil (SAF). COC-induced hypercholesterolemia was associated with elevations in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Saturated fat feeding also resulted in th saturation of fatty acids of triglycerides and cholesteryl esters of VLDL and LDL, but had little effect on HDL fatty acids. Lipoprotein composition and size were not influenced by the type of dietary fat, suggesting that the hypercholesterolemia with saturated fat feeding was due to the circulation of a greater number of lipoprotein particles. The apoproteins of gerbil lipoproteins had molecular weights comparable to other animals. The relative amounts of apoproteins, particularly the apoC peptides, increased with dietary fat saturation.

Animals↗
PubMed1981

Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. III. Biochemical and morphometric parameters of the liver.

The purpose of this study was to explore in rats the possible influence of the type of dietary fat at two extreme levels of vitamin E on several biochemically determined hepatic changes and on a number of quantitatively analyzed structural and ultrastructural variations with age in hepatic cells. Six groups of weanling Wistar male rats were fed ad libitum isoenergetic diets containing similar amounts (15 g per 100 g diet) of saturated fat (coconut oil), unsaturated fat (safflower oil) or a combination of both at two levels of dl-alpha-tocopherol (2 or 200 mg per 100 g of diet). Determinations were performed in rats killed at 3, 6, 12, 18 and 24 months. Although in relation to age and irrespective of the type of diet, several of the biochemical parameters fluctuated with time, comparisons of the results between the youngest and oldest rats showed no changes in the levels of hepatic RNA, phospholipids, cholesterol, total tocopherols and total collagens, significant increases in DNA and triglycerides and a significant decrease in total protein. While the type of diet did not have in general significant influences on the levels of DNA, RNA, total protein and collagens, either the type of dietary fat and/or the levels of vitamin E had some definite effects on the levels of triglycerides, cholesterol, phospholipids and total tocopherols, as well as on the in vitro formation of malonaldehyde and on the eventual occurrence of in vivo lipoperoxidation (diene conjugation). These effects, however, varied in relation to the duration of the diverse dietary treatments. The morphologic studies indicated that all the livers had variable but generally moderate degrees of fatty changes (mainly due to triglyceride accumulation) which were attributed to the moderate obesity found in the rats. The mean nuclear and cell dimensions of hepatocytes, the number of binucleated hepatocytes, surface density of rough endoplasmic reticulum, numerical density of mitochondria and the fractional cytoplasmic volume occupied by lipofuscin pigment in hepatocytes were not significantly affected by the type of diet, by age or by the eventual occurrence of in vivo hepatic lipoperoxidation, whereas the numerical density of hepatocytes (mono- and binucleated) and "litoral cells" (endothelial, Kupffer and Ito cells), although unaffected by diet, significantly increased with age. On the other hand, the fractional volume of mitochondria and peroxisomes, as well as the numerical density of peroxisomes, were significantly influenced by the type of dietary fat and to lesser extent by the dietary levels of vitamin E.

Aging↗
PubMed2004

Prevalence of obesity in south-east Spain and its relation with social and health factors.

Recent studies have confirmed important regional differences in the prevalence of obesity, as well as a tendency for this prevalence to increase. Determination of the social factors involved in obesity may be very useful to design intervention and prevention strategies. This transverse study was undertaken in Pizarra (Malaga, Spain) from a random sample of the population between 18 and 65 years of age (n = 1226). All participants were interviewed and given a physical examination. Standardized anthropometrical measurements were made, and a baseline blood sample was taken after an oral glucose tolerance test. The overall prevalence of obesity (BMI > 30 kg/m2) was 28.8%. This figure increased continuously from 10% in the group aged 18-25 years to above 50% in the groups aged over 55 years. This prevalence is higher than that reported in most other studies in Spain. The obese persons ate differently, at least from a qualitative viewpoint, probably more saturated fats and fewer unsaturated fats, and had a different behaviour concerning alcohol and smoking. Marital status was related with the rate of obesity, and the close relation between the level of education and the risk of obesity was confirmed (OR = 3.8 for being obese and having no education compared to having university studies). The most important consequence of the study was that all these factors are potentially modifiable and preventable. An increased level of general education in the population may well contribute decisively to a reduction in the prevalence of obesity.

Adolescent↗
PubMed1996

Fat intake of women during normal pregnancy: relationship with maternal and neonatal essential fatty acid status.

OBJECTIVE: To study the relationships between the essential fatty acid (EFA) composition of maternal diet, maternal EFA status and the EFA status of healthy newborn infants. METHODS: A prospective longitudinal study was performed in which 176 pregnant women completed a food frequency questionnaire (FFQ) before 13, at 22, and at 32 weeks of gestation, so that changes in nutrient intake throughout pregnancy could be recorded. Around 22 weeks, a dietary history was performed and a maternal blood sample was collected. Immediately after delivery, a blood sample from the umbilical vein and a piece of the umbilical cord were collected. Fatty acid compositions were determined for phospholipids (PLs) isolated from maternal and umbilical plasma and from umbilical vein and artery vessel walls. RESULTS: No significant differences in the mean daily intake of total fat, saturated fat, mono-unsaturated fat, polyunsaturated fat and linoleic acid (18:2(n-6), LA) were observed between the three trimesters. Maternal LA intake was positively associated with LA levels in maternal and umbilical plasma and negatively associated with 20:3(n-9), 18:3(n-3), 20:4(n-3) and 22:5(n-3) levels in maternal plasma, with 20:5(n-3) levels in umbilical plasma and with 22:6(n-3) levels in umbilical vein vessel walls. Significant positive correlations for almost all (n-6) and (n-3) fatty acids were observed between maternal and umbilical plasma levels. CONCLUSIONS: The maternal dietary fat composition appears to be consistent during pregnancy. A high maternal LA intake may have a lowering effect on the maternal as well as on the neonatal (n-3) fatty acid status. Finally, neonatal EFA status is strongly related to maternal EFA status.

Adult↗
PubMedDate not supplied

Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation.

OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.

Adult↗
PubMed1996

Dietary and exercise assessment in general practice.

BACKGROUND: Diet and physical activity are important in many conditions managed in primary care. Dietary and physical activity assessment is complex, has inherent inaccuracies related to self-reporting, and is only a small part of a larger context of developing effective intervention in primary care. However, for personalized assessment in routine clinical care, and for the assessment of different intervention strategies in a general practice research setting, validated life-style assessment tools are needed. OBJECTIVE: We aimed to discuss the requirements for assessment tools and to identify feasible validated assessment instruments for use in primary care. METHOD: Potential tools were identified from a Medline search, UK Research Intelligence, and contact with groups known to be working in the area. RESULTS: Several brief instruments assess mainly fat in the US diet, but the limited range of foods covered and the setting of studies limits their generalizability. Only one tool developed for UK use--'DINE', which scores total fat, fibre and unsaturated fat--was identified which is both feasible and has documented reasonable validated characteristics. Even for this tool there are doubts about the validation "standard'. No diet or physical activity validation studies have used both subjects and health professionals from general practice settings. CONCLUSION: There are very few feasible and validated dietary or physical activity assessment tools for use in clinical care or research in general practice, and doubts about the design and settings of published validation studies. Further research is needed to validate and develop a range of feasible life-style assessment tools with specified time and training requirements for use in primary care.

Exercise↗
PubMed2006

A comparison of two dietary instruments for evaluating the fat-breast cancer relationship.

BACKGROUND: Previous research suggests food diaries may be more efficient than food frequency questionnaires (FFQ) in detecting a dietary fat-breast cancer relationship. We assessed this further using 4 day food records (FRs) and FFQs in a large sample. METHODS: Participants were from the non-intervention group of the dietary modification component of the Women's Health Initiative Clinical Trial: 603 breast cancer cases and 1206 controls matched on age, clinic, and length of follow-up. Relative risks (RRs) were estimated using unconditional logistic regression, adjusted for confounders and for the selection into the trial of women with an FFQ report exceeding 32% calories from fat. Direct comparison of the statistical power of the two instruments used the standardized log RR. An alternative analysis after removing subjects with missing covariate data was also conducted. RESULTS: The RR estimate for breast cancer in the top quintile of total fat intake, adjusted for confounders and total energy, was 1.82 (P for trend 0.02) for the FR but 0.67 for the FFQ (P for trend 0.24). Following adjustment for selection, estimates were 2.09 (P for trend 0.008) for the FR (alternative: 2.54, P for trend 0.006) and 1.71 (P for trend 0.18) for the FFQ (alternative: 1.24, P for trend 0.41). Similar results were seen for fat subtypes, particularly unsaturated fats. Comparisons showed higher statistical power for the FR than the FFQ (e.g. total fat, P = 0.08: alternative P = 0.01). CONCLUSIONS: Alternative instruments, such as FRs, may be preferable to FFQs for evaluating diet-disease relationships in cohort studies. The results support a positive association between dietary fat and breast cancer.

Aged↗
PubMed1979

Effects of quantity and unsaturation of dietary fat on serum components in normal and diabetic Macaca nigra.

Dietary fat affects serum lipids independently of dietary cholesterol. Normal and diabetic monkeys (Macaca nigra) were fed cereal-based, specially formulated diets with either a low fat (LF = 2.5%) or a higher fat (13.2%) content; the latter had varying concentrations of safflower and coconut oil to attain greater polyunsaturation (SFO) or saturation (CCO) in the diets. Dietary cholesterol was less than 0.01%. Serum triglyceride concentrations were greatest when monkeys consumed the LF (higher carbohydrate) diet and lowest when they consumed the SFO diet. Concentrations were greater in diabetic than in normal monkeys fed the LF and SFO diets, but both groups had similar concentrations when fed the CCO diet. Cholesterol levels in diabetic monkeys were only slightly higher than in normals regardless of diet; in both groups, levels were lowest when the LF diet was fed and highest when the CCO diet was fed. The quantity of fat had a greater effect on serum cholesterol than did the degree of polyunsaturation. In both groups, triglyceride concentrations correlated significantly with VLDL protein, and cholesterol levels correlated with LDL protein. Thus the responses of Macaca nigra to dietary fat manipulation depend upon both the diet fat content and composition as well as the normal or diabetic metabolic state of each monkey.

Animals↗
PubMedDate not supplied

Effects of selective breeding on the cholesterolemic responses to dietary saturated fat and cholesterol in baboons.

Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat-enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol.

Age Factors↗
PubMed1974

Fatty acid-binding protein in small intestine. Identification, isolation, and evidence for its role in cellular fatty acid transport.

A soluble fatty acid-binding protein (FABP), mol wt approximately 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro.FABP was isolated from rat intestine by gel filtration and isoelectric focusing. It showed a reaction of complete immunochemical identity with proteins in the 12,000 mol wt fatty acid-binding fractions of liver, myocardium, and adipose tissue supernates. (The presence of immunochemically nonidentical 12,000 mol wt FABP in these tissues is not excluded.) By quantitative radial immunodiffusion, supernatant FABP concentration in mucosa from proximal and middle thirds of jejuno-ileum significantly exceeded that in distal third, duodenum, and liver, expressed as micrograms per milligram soluble protein, micrograms per gram DNA, and micrograms per gram tissue. FABP concentration in villi was approximately three times greater than in crypts. Small quantities of FABP were present in washed nuclei-cell membrane, mitochondrial and microsomal fractions. However, the amount of FABP solubilized per milligram membrane protein was similar for all particulate fractions, and total membrane-associated FABP was only about 16% of supernatant FABP. Intestinal FABP concentration was significantly greater in animals maintained on high fat diets than on low fat; saturated and unsaturated fat diets did not differ greatly in this regard.The preponderance of FABP in villi from proximal and middle intestine, its ability to bind fatty acids in vivo as well as in vitro, and its response to changes in dietary fat intake support the concept that this protein participates in cellular fatty acid transport during fat absorption. Identical or closely related 12,000 mol wt proteins may serve similar functions in other tissues.

Adipose Tissue↗
PubMed2001

Effects of choice white grease or poultry fat on growth performance, carcass leanness, and meat quality characteristics of growing-finishing pigs.

Eighty-four crossbred gilts were used to evaluate the effects of dietary choice white grease (CWG) or poultry fat (PF) on growth performance, carcass characteristics, and quality characteristics of longissimus muscle (LM), belly, and bacon of growing-finishing pigs. Pigs (initially 60 kg) were fed a control diet with no added fat or diets containing 2, 4, or 6% CWG or PF. Diets were fed from 60 to 110 kg and contained 2.26 g lysine/Mcal ME. Data were analyzed as a 2 x 3 factorial plus a control with main effects of fat source (CWG and PF) and fat level (2, 4, and 6%). Pigs fed the control diet, 2% fat, and 4% fat had greater (P < 0.05) ADFI than pigs fed 6% fat. Pigs fed 6% fat had greater (P < 0.05) gain/feed (G/F) than pigs fed the control diet or other fat levels. Subcutaneous fat over the longissimus muscle from pigs fed CWG had more (P < 0.05) moisture than that from pigs fed PF. Feeding dietary fat (regardless of source or level) reduced (P < 0.05) the amount of saturated fats present in the LM. Similarly, 4 or 6% fat decreased (P < 0.05) the amount of saturated fats and increased unsaturated fats present in the bacon. No differences (P > 0.05) were observed for ADG, dressing percentage, leaf fat weight, LM pH, backfat depth, LM area, percentage lean, LM visual evaluation, LM waterholding capacity, Warner-Bratzler shear and sensory evaluation of the LM and bacon, fat color and firmness measurements, or bacon processing characteristics. Adding dietary fat improved G/F and altered the fatty acid profiles of the LM and bacon, but differences in growth rate, carcass characteristics, and quality and sensory characteristics of the LM and bacon were minimal. Dietary additions of up to 6% CWG or PF can be made with little effect on quality of pork LM, belly, or bacon.

Adipose Tissue↗
PubMedDate not supplied

Dietary markers of hypertension associated with pulse pressure and arterial compliance in black South African children: the THUSA Bana Study.

AIM: The aim of the study was to determine which dietary factors contribute to the impairment of arterial compliance, stroke volume, total peripheral resistance and pulse pressure, and could thereby be identified as risk markers in the development of hypertension in black children. METHODS: Children aged 10 to 15 years were recruited from 30 schools in the North West Province over two years (2000 to 2001). These children comprised 321 black males and 373 females from rural to urbanised communities and 40 male and 79 females subjects with identified high-normal to hypertensive blood pressure. Blood pressure was measured by means of a Finapres apparatus. Through analysis with the Fast Modelflo software program, systemic arterial compliance, pulse pressure, total peripheral resistance and stroke volume were obtained. A 24-hour dietary recall questionnaire and weight and height measurements were taken. RESULTS: In a stepwise regression analysis the following nutrient were significantly associated (p < or = 0.05) with cardiovascular parmeters of hypertensive subjects: protein, carbohydrates, total fat, polyunsaturated fat, mono-unsaturated fat, saturated fat, fibre, vitamin A, nicotinic acid, biotin, vitamin B(12), ascorbic acid, vitamin E, magnesium, manganese, phoshorus and iron. No significant dietary markers were indicated for the normotensive groups. Dietary intakes of most of these nutrients were below the dietary reference intakes for all groups. CONCLUSIONS: The results indicate strong associations of protein, polyunsaturated fats, fibre, vitamin A, vitamin C, vitamin E, nicotinic acid, vitamin B(12), biotin and phosphorus with the rate of hypertension in black South African children.

Adolescent↗
PubMed1986

Effects of high levels of dietary fats on the growth of azaserine-induced foci in the rat pancreas.

Azaserine induced two phenotypically different populations of foci, namely, acidophilic and basophilic foci. The effects of dietary modification during the post-initiation phase of carcinogenesis were examined. A diet of 20% (w/w) unsaturated fat (unsat) compared to a 20% saturated fat (sat) diet or a control diet (5% unsaturated fat) increased the number of acidophilic foci, as well as the thymidine labeling index (LI) of their nuclei. While the basophilic foci are carcinogen-induced and at 2.5 mo post-initiation have a similarly high growth rate to the acidophilic foci, this rate is not sustained as indicated by examination of both the LI and mean size of foci at 4 mo post-initiation.

Animals↗