Dataset Information

Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

ABSTRACT: Bile acid (BA) sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG) levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY). Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt) gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7?-hydroxylase (Cyp7a1), compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and complementary efficacy as a lipid-lowering combination therapy in conjunction with CHY by attenuating hepatic cholesterol synthesis, enhancing BA biosynthesis and decreasing lipogenesis, which warrants further investigation.

SUBMITTER: Heidker RM

PROVIDER: S-EPMC4844140 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

Heidker Rebecca M RM Caiozzi Gianella C GC Ricketts Marie-Louise ML

PloS one 20160425 4

Bile acid (BA) sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG) levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG ...[more]

PMID: 27111442

Similar Datasets

Project description:The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for reducing hypertriglyceridemia and hepatic lipid accumulation in the presence of fructose.

Project description:BackgroundIn people, bile acid diarrhoea is a prevalent complication of Crohn's disease and diarrhoea-associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well.Case descriptionsTwo dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs.ConclusionThis report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea.

Project description:BackgroundObesity has one of the highest refractory rates of all chronic diseases, in part because weight loss induced by calorie restriction, the first-line treatment for obesity, elicits biological adaptations that promote weight regain. Although acute feeding trials suggest a role for macronutrient composition in modifying brain activity related to hunger and satiety, relevance of these findings to weight-loss maintenance has not been studied.ObjectivesWe investigated effects of weight-loss maintenance diets varying in macronutrient content on regional cerebral blood flow (rCBF) in brain regions involved in hunger and reward.MethodsIn conjunction with a randomized controlled feeding trial, we investigated the effects of weight-loss maintenance diets varying in carbohydrate content [high, 60% of total energy: n = 20; 6 men/14 women; mean age: 32.5 y; mean BMI (in kg/m 2): 27.4; moderate, 40% of total energy: n = 22; 10 men/12 women; mean age: 32.5 y; mean BMI: 29.0; low, 20% of total energy: n = 28; 12 men/16 women; mean age: 33.2 y; mean BMI: 27.7] on rCBF in brain regions involved in hunger and reward preprandial and 4 h postprandial after 14-20 wk on the diets. The primary outcome was rCBF in the nucleus accumbens (NAcc) at 4 h postprandial; the secondary outcome was preprandial rCBF in the hypothalamus.ResultsConsistent with a priori hypothesis, at 4 h postprandial, NAcc rCBF was 43% higher in adults assigned to the high- compared with low-carbohydrate diet {P[family-wise error (FWE)-corrected] < 0.05}. Preprandial hypothalamus rCBF was 41% higher on high-carbohydrate diet [P(FWE-corrected) < 0.001]. Exploratory analyses revealed that elevated rCBF on high-carbohydrate diet was not specific to prandial state: preprandial NAcc rCBF [P(FWE-corrected) < 0.001] and 4 h postprandial rCBF in hypothalamus [P(FWE-corrected) < 0.001]. Insulin secretion predicted differential postprandial activation of the NAcc by diet.ConclusionsWe report significant differences in rCBF in adults assigned to diets varying in carbohydrate content for several months, which appear to be partially associated with insulin secretion. These findings suggest that chronic intake of a high-carbohydrate diet may affect brain reward and homeostatic activity in ways that could impede weight-loss maintenance. This trial was registered at clinicaltrials.gov as NCT02300857.

Dataset Information

Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

Publications

Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets