deoxycholic-acid and Weight-Gain

Metabolic syndrome is characterized by low-grade chronic systemic inflammation, which is associated with intestinal hyperpermeability. This study examined the effects of 3 high-fat diets (HFDs) composed of different fat sources (soybean oil and lard) on the intestinal permeability, tight junction (TJ) protein expression, and cecal bile acid (BA) concentrations in mice, and then analyzed their interrelations. C57/BL6 mice were fed the control diet, HFD (soybean oil), HFD (lard), and HFD (mix; containing equal concentrations of soybean oil and lard) for 8 wk. Glucose tolerance, intestinal permeability, TJ protein expression, and cecal BA concentration were evaluated. Feeding with the 3 HDFs similarly increased body weight, liver weight, and fat pad weight, and induced glucose intolerance and intestinal hyperpermeability. The expression of TJ proteins, zonula occludens-2 and junctional adhesion molecule-A, were lower in the colons of the 3 HFD groups than in the control group (P < 0.05), and these changes appeared to be related to intestinal hyperpermeability. Feeding with HFDs increased total secondary BA (SBA) and total BA concentrations along with increases in some individual BAs in the cecum. Significant positive correlations between intestinal permeability and the concentrations of most SBAs, such as deoxycholic acid and ω-muricholic acids, were detected (P < 0.05). These results suggest that the HFD-induced intestinal hyperpermeability is associated with increased BA secretion. The abundance of SBAs in the large intestine may be responsible for the hyperpermeability.

Topics: Adipose Tissue; Animals; Bile Acids and Salts; Cecum; Cholic Acids; Colon; Deoxycholic Acid; Diet, High-Fat; Dietary Fats; Inflammation; Intestinal Diseases; Intestine, Large; Junctional Adhesion Molecules; Liver; Male; Metabolic Syndrome; Mice, Inbred C57BL; Soybean Oil; Tight Junctions; Weight Gain; Zonula Occludens-2 Protein

The objective of the present experiment was to investigate whether deoxycholate and cholate would differ in their effectiveness of counteracting the inhibitory effect of calcium on fat digestibility in rats. Rats were fed one of four experimental diets, a diet low in calcium, high in calcium or high in calcium with either 0.5% sodium cholate or 0.5% sodium deoxycholate. Both deoxycholate and cholate supplementation of the high-calcium diet reduced feed intake and body-weight gain. Low-calcium intake increased fat digestibility. Supplemental bile acids partially counteracted the calcium-induced inhibition of fat digestion, cholate being more effective than deoxycholate. The outcome is explained by the suggestion that cholate is bound to the calcium phosphate sediment in the small intestinal lumen with less affinity than deoxycholate. As a result, more cholate than deoxycholate would be available to support the process of fat digestion. Rats fed cholate had higher liver and serum cholesterol concentrations than did the rats fed deoxycholate.

Topics: Animals; Calcium; Calcium, Dietary; Cholates; Cholesterol; Deoxycholic Acid; Dietary Fats; Digestion; Dose-Response Relationship, Drug; Male; Random Allocation; Rats; Rats, Wistar; Weight Gain

Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

Topics: Adenoma; Animals; Bile Acids and Salts; Calcium; Colon; Colorectal Neoplasms; Deoxycholic Acid; Diet; Disease Models, Animal; Epithelium; Fatty Acids; Female; Rats; Rats, Sprague-Dawley; Weight Gain

Bile acid composition, synthetic rate and pool size were determined in rats fed diets containing 5 g cellulose, 5 g pectin or 5 g psyllium hydrocolloid/100 g diet using the washout technique. Bile acid pool sizes were similar for pectin- and psyllium-fed rats, and both were higher than the pool size for rats fed cellulose (5.48 +/- 1.22, 4.70 +/- 0.71 and 1.77 +/- 0.41 mumol/100 g body wt, respectively). Bile acid secretion rates showed a similar pattern [1730 +/- 496, 1551 +/- 252 and 572 +/- 88 nmol/(h.100 g body wt)], as did basal synthetic rates [129 +/- 25, 126 +/- 42 and 87 +/- 18 pmol/(h.100 g body wt)]. Individual and total bile acid pool sizes were generally higher in animals fed the pectin- or psyllium-supplemented diet compared with rats fed cellulose. Pectin or psyllium consumption resulted in a lower hydrophobicity of the bile acid pool and a lower ratio of circulating 12 alpha-hydroxylated to non-12 alpha-hydroxylated bile acids compared with cellulose consumption. This reduced hydrophobicity has been shown to reduce feedback inhibition of bile acid synthesis and may be responsible for the larger bile acid pool size. Changes in the location of reabsorption of bile acids may also be responsible for changes in the pool size and composition. These changes are characteristic of greater sterol excretion.

Topics: Animals; Bile; Bile Acids and Salts; Chemical Phenomena; Chemistry, Physical; Colloids; Deoxycholic Acid; Dietary Fiber; Intestinal Absorption; Male; Pectins; Psyllium; Rats; Rats, Wistar; Weight Gain

The purpose of this study was to determine the effect of different amounts of dietary fat on colonic cell proliferation and fecal bile acid concentrations. Thirty-nine male Sprague-Dawley rats were randomly assigned to three diets (13 rats per diet) containing 5, 10 and 20 g butter/100 g diet. Diets were fed for 3 wk. As fat intake increased, total fecal fat excretion remained constant. When dietary fat was decreased from 20 to 10 g/100 g diet, total fecal bile acid concentrations tended to increase 14.5%. However, a further reduction to 5 g butter/100 g diet significantly decreased fecal total bile acid concentration by 48% from the concentration in feces of rats fed 10 g butter/100 g diet. The concentration of deoxycholate (considered a highly promotive bile acid) was not reduced unless the amount of fat in the diet was reduced to 5 g/100 g. Labeling index was used as an intermediate marker for colon carcinogenesis. For deoxycholate, a decrease of fat intake to 5 g/100 g diet decreased the cecal labeling index relative to those of rats fed 10 or 20 g butter/100 g diet. These data indicate that decreasing the dietary fat from 20 to 10 g/100 g does not decrease fecal bile acid concentration or colonic cell proliferation, but some effects are seen in rats fed 5 g butter/100 g diet.

Topics: Animals; Bile Acids and Salts; Butter; Cell Division; Colon; Deoxycholic Acid; Dietary Fats; Eating; Energy Intake; Feces; Hydrogen-Ion Concentration; Intestine, Large; Lipids; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Weight Gain

The antitumorigenic effect of cryptoporic acid E (CPA-E), a dimeric drimane sesquiterpenoid isolated from the fungus Cryptoporus volvatus, on colon carcinogenesis was investigated. Female F344 rats given an intrarectal instillation of 2 mg of N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 were fed diet containing 0.2% CPA-E from week 3. Female ICR mice given 15 weekly intraperitoneal injections of 10 mg of 1,2-dimethylhydrazine/kg body weight during weeks 1 to 15 were fed diet containing 0.06% CPA-E from week 1. The experiment was terminated at week 35 for rats and at week 25 for mice. The incidence and the number of tumors per animal were reduced in CPA-E-fed animals compared to the controls: 31% vs. 75% (P less than 0.05) and 0.4 +/- 0.2 (SEM) vs. 0.9 +/- 0.2 (0.1 greater than P greater than 0.05) in rats, and 31% vs. 63% (0.1 greater than P greater than 0.05) and 0.4 +/- 0.2 vs. 2.4 +/- 0.8 (P less than 0.05) in mice (16 animals in each group). Intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity was significantly lowered in CPA-E-fed animals compared to controls. This shows an antipromoting activity of CPA-E against colon carcinogenesis. Thus, it was concluded that CPA-E inhibits colon cancer development in both rats and mice treated with 2 different colon carcinogens.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Biomarkers, Tumor; Carcinogens; Colon; Colonic Neoplasms; Deoxycholic Acid; Dimethylhydrazines; Enzyme Induction; Feeding Behavior; Female; Intestinal Mucosa; Methylnitrosourea; Mice; Mice, Inbred ICR; Ornithine Decarboxylase; Polyporaceae; Rats; Rats, Inbred F344; Sesquiterpenes; Weight Gain