linoleic-acid and Hyperplasia

Little evidence exists concerning the effects of trans-10,cis-12 conjugated linoleic acid (CLA) under energy restriction. Thus, the effects of this CLA isomer on adipose tissue size, liver composition, as well as on expression and activity of carnitine-palmitoyl transferase I (CPT-I) and acyl CoA oxidase (ACO), in hamsters fed an energy-restricted diet were analyzed.. Hamsters were fed a high-fat diet for 7 wk and then subjected to 25% energy-restricted diets supplemented with 0.5% linoleic acid or 0.5% trans-10,cis-12 CLA for 3 wk. Serum insulin, free-triiodothyronine and non-esterified fatty acid levels, liver triacylglycerol, protein and water contents, and CPT-I, ACO, and Peroxisome proliferator-activated receptor alpha (PPARα) expressions and enzyme activities were assessed.. Energy restriction reduced liver size, serum levels of insulin, free-triiodothyronine, and non-esterified fatty acid and increased CPT-I activity. Liver composition was not modified. No differences were found between both restricted groups, with the exception of CPT-I and ACO oxidative enzyme activities, which were greater in hamsters fed the CLA diet.. Energy restriction does not cause trans-10,cis-12 CLA to induce liver hyperplasia. Although this CLA isomer increases liver CPT-I and ACO activities, this effect does not result in reduced hepatic triacylglyerol content or decreased adipose tissue size. Consequently, this CLA isomer seems not to be a useful tool for inclusion in body weight loss strategies followed during obesity treatment.

Topics: Acyl-CoA Oxidase; Animals; Caloric Restriction; Carnitine O-Palmitoyltransferase; Cricetinae; Dietary Fats; Dietary Supplements; Fatty Acids, Nonesterified; Hyperplasia; Insulin; Isomerism; Linoleic Acid; Linoleic Acids, Conjugated; Lipid Peroxidation; Liver; Male; Mesocricetus; Obesity; Triiodothyronine

To study the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on liver size and composition, as well as on hepatic lipogenesis and fatty acid oxidation, in adult hamsters.. Sixteen male Syrian Golden hamsters (8-month-old; initial body weight 167 +/- 5 g) were divided into two groups and fed on atherogenic diets supplemented either with 0.5% linoleic acid or trans-10,cis-12 CLA, for 6 weeks. Liver lipids, fatty acid profile, protein, water and DNA contents were analysed. The activity and expression of several enzymes involved in liver fatty oxidation and lipogenesis were assessed, as was the expression of transcriptional factors controlling these enzymes.. The addition of CLA to the diet led to significantly greater liver weight due to hyperplasia. No changes were observed in liver composition. CLA did not modify the expression or the activity of analysed oxidative enzymes. With regard to lipogenic enzymes, an increase in the expression and the activity of acetyl-CoA carboxylase was found.. These results show that the expected body fat-lowering effect of trans-10,cis-12 CLA, observed in young rodents, is not found in adult hamsters. The lack of increase in liver fatty acid oxidation, help to explain why that effect was not found in these animals. Further, the CLA treatment-induced hepatomegaly is a consequence of hyperplasia.

Topics: Acetyl-CoA Carboxylase; Age Factors; Animals; Cricetinae; Diet, Atherogenic; Dietary Fats; Fatty Liver; Hepatomegaly; Hyperplasia; Linoleic Acid; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Mesocricetus; Organ Size; Oxidoreductases

The role of enteral or parenteral long-chain triacylglycerol (LCT) in the complex process of intestinal adaptation is poorly defined and may involve alterations in eicosanoid synthesis. Our objective was to determine whether provision of parenteral LCT stimulates eicosanoid synthesis and resection-induced intestinal adaptation. We assessed small bowel structural adaptation, the fatty acid profiles of liver, plasma and jejunal mucosa, and the profile of 11 eicosanoids derived from (n-6) PUFA of the jejunal mucosa in rats maintained with total parenteral nutrition (TPN) with 0 or 32% of nonprotein energy from Intralipid for 7 d after mid-small bowel resection or transection control surgery. There was no evidence of biochemical essential fatty acid (EFA) deficiency in the absence of parenteral fat. Resection-induced gut growth occurred independently of parenteral LCT based on significant mucosal hyperplasia in the jejunum and ileum. The mucosal profile of linoleic acid in the total lipid extract of jejunum increased with the presence of parenteral LCT, but decreased with resection without differences in arachidonic acid. There were no differences in the jejunal profile of 11 (n-6)-derived eicosanoids among the four TPN groups as determined by tandem MS. In summary, small bowel resection-induced adaptation occurs independently of parenteral LCT, and fat-free TPN without EFA deficiency does not alter the profile of jejunal (n-6)-derived eicosanoids. Thus, parenteral administration of LCT does not appear to alter jejunal eicosanoid synthesis nor is it beneficial in stimulating intestinal adaptation.

Topics: Adaptation, Physiological; Dietary Fats; Dinoprost; Dinoprostone; Eicosanoids; Fatty Acids; Hyperplasia; Ileum; Intestinal Mucosa; Intestine, Small; Intestines; Jejunum; Linoleic Acid; Lipids; Liver; Oleic Acid; Palmitic Acid; Parenteral Nutrition, Total; Triglycerides; Weight Gain

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

Topics: 1,2-Dimethylhydrazine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; Female; Glutathione Transferase; Hyperplasia; Linoleic Acid; Mammary Neoplasms, Experimental; Neoplasms; Nitrosamines; Organ Size; Phosphorylation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Safflower Oil; Time Factors; Urinary Bladder Neoplasms

Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits phorbol ester-induced skin tumor promotion in mice. The goal of the present study was to determine potential chemoprotective mechanisms through which CLA may be acting. Mice were fed diets containing 0.0%, 0.5%, 1.0%, or 1.5% CLA (by wt) for six weeks. The epidermis was evaluated for fatty acid composition, vascular permeability, prostaglandin E2 (PGE2) production, hyperplasia, ornithine decarboxylase activity, and c-myc mRNA accumulation. Fatty acid analysis of mouse epidermis demonstrated a dose-dependent increase of CLA incorporation into phospholipids and neutral lipids. In mice topically treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), dietary CLA (1.5%) significantly (p < 0.05) reduced PGE2 synthesis (2-fold). Additionally, CLA lowered accumulation of c-myc mRNA, a gene commonly associated with regulating cell cycle components involved in cellular proliferation, although this trend was not significant. Vascular permeability was unaffected by dietary CLA. These data suggest that dietary CLA modulates TPA-induced tumor promotion through a mechanism involving PGE2 production; however, dietary CLA had a moderate effect on c-myc mRNA levels and little effect on TPA-induced hyperplasia and ornithine decarboxylase activity.

Topics: Analysis of Variance; Animals; Anticarcinogenic Agents; Capillary Permeability; Dietary Fats; Dinoprostone; DNA Primers; Dose-Response Relationship, Drug; Epidermis; Female; Genes, myc; Hyperplasia; Linoleic Acid; Mice; Mice, Inbred Strains; Ornithine Decarboxylase; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms; Tetradecanoylphorbol Acetate

Topics: Animals; Aorta; Catheterization; Cholesterol, Dietary; Diet, Atherogenic; Dietary Supplements; Hypercholesterolemia; Hyperplasia; Linoleic Acid; Male; Rabbits; Tunica Intima

Potential promoting effects of alpha-linolenic, linoleic and palmitic acids were investigated in a two-stage urinary bladder carcinogenesis model. In experiment 1, male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and then basal diet containing 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in the urinary bladder was not increased by treatment with any of the fatty acids. In experiment 2, male F344 rats were given 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN treatment. The administration of fatty acids was not associated with any increase in the 5-bromo-2'-deoxyuridine labeling index of the urinary bladder epithelium. Serum and/or urine fatty acid levels increased in the cases of alpha-linolenic and linoleic acid treatments, but not with palmitic acid. Under the present experimental conditions neither the two polyunsaturated nor the one saturated fatty acid exerted any promoting effect on urinary bladder carcinogenesis.

Topics: alpha-Linolenic Acid; Animals; Butylated Hydroxyanisole; Butylhydroxybutylnitrosamine; Hyperplasia; Kidney; Linoleic Acid; Linoleic Acids; Male; Organ Size; Palmitic Acid; Palmitic Acids; Rats; Rats, Inbred F344; Urinary Bladder; Urinary Bladder Neoplasms

Pseudo-acylceramides with different acyl properties were investigated for their capacity to restore diminished barrier function in essential fatty acid-deficient rats. Daily topical applications of synthetic pseudo-acylceramides containing ester-linked linoleic acid caused a dose-dependent, significant reduction of transepidermal water loss (TEWL). Both other pseudo-acylceramides with ester-linked oleic acid or saturated alkyl chains and ordinary ceramides exhibited a poor effect on recovery of TEWL. Furthermore, pseudoceramide containing ether-linked linoleic acid, which is biologically inactive in terms of degradation by hydrolytic enzymes, also induced a significant and similar increase in the barrier function. This restoration of barrier function by pseudo-acylceramides with linoleic acid was accompanied by suppressed DNA synthesis in the EFAD rat epidermis. In UVB-irradiated guinea pig skin, topical applications of the pseudo-acylceramides with linoleic acid immediately after the exposure significantly reduced epidermal hyperplasia, secondary to markedly diminished barrier disruption, whereas linoleic acid itself did not. A comparison of both the anti-hyperplasia and the barrier recovery effects in the series of pseudo-ceramide derivatives examined revealed that the suppressive effect on the induced epidermal hyperplasia was paralleled by the recovery of the barrier defect in EFAD rats. These findings directly suggest that acylceramide with an ester-linked linoleic acid has an essential role in the epidermal permeability barrier.

Topics: Animals; Cells, Cultured; Ceramides; DNA; Epidermis; Fatty Acids, Essential; Guinea Pigs; Humans; Hyperplasia; Keratinocytes; Linoleic Acid; Linoleic Acids; Male; Permeability; Rats; Rats, Wistar

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.

Topics: Animals; Ceruletide; Chronic Disease; Disease Models, Animal; Drug Combinations; Exocrine Pancreatic Insufficiency; Hyperplasia; Linoleic Acid; Linoleic Acids; Male; Oleic Acid; Oleic Acids; Pancreas; Rats; Rats, Inbred Strains; Zein