phytosterols and Weight-Gain

The aim of this study is to investigate the mechanism of anti-obesity effects of Aloe vera gel extract (AVGE) containing Aloe sterols. Previously, we reported that oral intake of Aloe vera components has an anti-diabetic and anti-obesity effect. This study was designed to assess the role of brown adipose tissue (BAT) in the anti-obesity effect of AVGE. Six-week-old male mice were divided into three groups; STD (standard diet), HFD (60% high fat diet) and AVGE (60% high fat diet with AVGE treatment). During 11 wk of AVGE administration, body weight has been monitored. Tissue samples were obtained to be measured the weight and evaluated the gene expressions. Mice treated with AVGE had suppressed body weight, and liver and fat weight gain. To investigate BAT activation, we measured the expression of mRNA related to BAT thermogenesis. Mice in the AVGE group had higher expression of Ucp1, Adrb3, and Cidea in BAT compared to HFD. Next, to investigate the possibility that AVGE induced hepatic FGF21, which is an important factor for nutrient and energy homeostasis including BAT regulation, in vitro study was conducted. HepG2 cell stimulated by AVGE were highly expressed FGF21. These results suggested that BAT activation partially contributes to mechanism of anti-obesity effect of Aloe sterols in diet-induced obesity (DIO) models. However, further study is needed to determine the predominant mechanism.

Topics: Adipose Tissue, Brown; Administration, Oral; Aloe; Animals; Anti-Obesity Agents; Diet, High-Fat; Dietary Fats; Energy Metabolism; Fibroblast Growth Factors; Hep G2 Cells; Humans; Liver; Male; Mice, Inbred C57BL; Obesity; Phytosterols; Phytotherapy; Plant Extracts; Plant Preparations; Thermogenesis; Weight Gain

Plants now supply more than 50 % of protein in Norwegian salmon aquafeeds. The inclusion of plant protein in aquafeeds may be associated with decreased lipid digestibility and cholesterol and bile salt levels, indicating that the replacement of fishmeal with plant protein could result in inadequate supplies of cholesterol in fish. A reduction in feed efficiency, fish growth and pathogen resistance is often observed in parallel to alterations in sterol metabolism. Previous studies have indicated that the negative effects induced by plant components can be attenuated when diets are supplemented with cholesterol. The present study evaluated the effects of dietary cholesterol supplementation (1·5 %) in Atlantic salmon fed a plant-based diet for 77 d. The weights of body, intestines and liver were recorded and blood, tissues, faeces, chyme and bile were sampled for the evaluation of effects on growth, nutrient utilisation and metabolism, and transcriptome and metabolite levels, with particular emphasis on sterol metabolism and organ structure and function. Cholesterol supplementation did not affect the growth or organ weights of Atlantic salmon, but seemed to promote the induction of cholesterol and plant sterol efflux in the intestine while suppressing sterol uptake. Cholesterol biosynthesis decreased correspondingly and conversion into bile acids increased. The marked effect of cholesterol supplementation on bile acid synthesis suggests that dietary cholesterol can be used to increase bile acid synthesis in fish. The present study clearly demonstrated how Atlantic salmon adjusted their metabolic functions in response to the dietary load of cholesterol. It has also expanded our understanding of sterol metabolism and turnover, adding to the existing, rather sparse, knowledge of these processes in fish.

Topics: Animals; Animals, Inbred Strains; Aquaculture; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Diet; Dietary Proteins; Energy Intake; Fish Proteins; Gene Expression Regulation, Developmental; Herbivory; Intestinal Absorption; Intestinal Mucosa; Intestines; Liver; Norway; Phytosterols; Plant Proteins; Random Allocation; Salmo salar; Weight Gain

Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms.

Topics: Alcohols; Animals; Diet, High-Fat; Energy Metabolism; Fatty Acids; Gastric Inhibitory Polypeptide; Hep G2 Cells; Humans; Intra-Abdominal Fat; Liver; Male; Mice, Inbred C57BL; Obesity; Oryza; Phytosterols; Phytotherapy; Postprandial Period; Triterpenes; Weight Gain

Replacing dietary fishmeal (FM) and fish oil (FO) with plant ingredients in Atlantic salmon (Salmo salar L.) diets decreases dietary cholesterol and introduces phytosterols. The aim of the present study was to assess the effect of dietary sterol composition on cholesterol metabolism in Atlantic salmon. For this purpose, two dietary trials were performed, in which Atlantic salmon were fed either 100 % FM and FO (FM-FO) diet or one of the three diets with either high (80 %) or medium (40 %) plant protein (PP) and a high (70 %) or medium (35 %) vegetable oil (VO) blend (trial 1); or 70 % PP with either 100 % FO or 80 % of the FO replaced with olive, rapeseed or soyabean oil (trial 2). Replacing ≥ 70 % of FM with PP and ≥ 70 % of FO with either a VO blend or rapeseed oil increased plasma and liver TAG concentrations. These diets contained high levels of phytosterols and low levels of cholesterol. Fish fed low-cholesterol diets, but with less phytosterols, exhibited an increased expression of genes encoding proteins involved in cholesterol uptake and synthesis. The expression of these genes was, however, partially inhibited in rapeseed oil-fed fish possibly due to the high dietary and tissue phytosterol:cholesterol ratio. Atlantic salmon tissue and plasma cholesterol concentrations were maintained stable independent of the dietary sterol content.

Topics: Animals; Aquaculture; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet; Dietary Proteins; Fatty Acids, Monounsaturated; Fish Proteins; Gene Expression Regulation, Developmental; Liver; Liver X Receptors; Olive Oil; Orphan Nuclear Receptors; Oxidoreductases Acting on CH-CH Group Donors; Phytosterols; Plant Oils; Plant Proteins; Rapeseed Oil; Salmo salar; Soybean Oil; Sterol Regulatory Element Binding Protein 2; Triglycerides; Weight Gain

Plant sterols, or phytosterols, are very similar in structure to cholesterol and are abundant in typical diets. The reason for poor absorption of plant sterols by the body is still unknown. Mutations in the ABC transporters G5 and G8 are known to cause an accumulation of plant sterols in blood and tissues (sitosterolemia). To determine the significance of phytosterol exclusion from the body, we fed wild-type and ABCG5/G8 knockout mice a diet enriched with plant sterols. The high-phytosterol diet was extremely toxic to the ABCG5/G8 knockout mice but had no adverse effects on wild-type mice. ABCG5/G8 knockout mice died prematurely and developed a phenotype that included high levels of plant sterols in many tissues, liver abnormalities, and severe cardiac lesions. This study is the first to report such toxic effects of phytosterol accumulation in ABCG5/G8 knockout mice. We believe these new data support the conclusion that plant sterols are excluded from the body because they are toxic when present at high levels.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Diet; Erythrocytes; Feeding Behavior; Gene Expression Regulation; Hepatomegaly; Lipoproteins; Liver; Mice; Mice, Knockout; Myocardium; Organ Size; Phytosterols; Spleen; Splenomegaly; Weight Gain

Previous research indicates that animals fed a high fat (HF) diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP) exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C). To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA) in the presence and absence of unesterified phytosterols (PS), and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group). In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation.

Topics: Adiposity; Animals; Ascorbic Acid; Calorimetry; Dietary Fats; Dietary Supplements; Drug Evaluation, Preclinical; Eating; Feces; Gastrointestinal Transit; Male; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Phytosterols; Weight Gain

Anti-obesity effects of a fermentation product of phytosterols including campestenone in ICR mice were investigated. Five-week-old male ICR mice were fed by the pair-feeding method for 8 wk. Experimental feed was prepared by adding TO-001, a phytostenone mixture produced by fermentation of phytosterols using Nocardioides simplex, at 0.25, 0.5, 1.0, or 2.0% or no additive to a high fat diet (fat 20%). Mice fed a stock feed (fat 5.6%) ad libitum were used as the standard growth group. In animals fed the high fat diet, control (no added TO-001) mice showed a weight gain that was about 10% higher than for the standard growth group. TO-001 reduced body weight dose-dependently. Final body weights of 0.5% and 1.0% TO-001-fed mice were lowered by about 9% and those of 2.0% TO-00 I-fed mice by about 12% compared with the control mice. Visceral and subcutaneous fat weight in mice fed TO-001 was significantly lower than that in mice fed the control diet. The concentrations of serum triglyceride (TG) and total cholesterol (TC) were significantly lower in the 1.0% and/or 2.0% TO-001-fed mice. Furthermore, levels of liver TG and TC were decreased in the TO-001-fed group. Increase of total lipid excretion in the feces was dose dependent. No obvious abnormalities due to consumption of TO-001 were detected by a blood biochemical examination, clinical observations or necropsy. The results suggested that TO-001, a fermentation product of phytosterols, may be a promising component of dietetic functional foods.

Topics: Adipose Tissue; Analysis of Variance; Animals; Biomarkers; Body Composition; Body Fat Distribution; Cholesterol; Dose-Response Relationship, Drug; Feces; Fermentation; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred ICR; Models, Animal; Phytosterols; Time Factors; Triglycerides; Weight Gain

In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil FA, plant sterols have recently been esterified to fish oil n-3 PUFA. The objective of this study was to determine the effects of plant sterols esterified to n-3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters were fed diets varying in cholesterol and plant sterol content: (i) Non-cholesterol (semipurified diet with no added cholesterol or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols), or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols). The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P = 0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters fed nonesterified plant sterols (P < 0.0001). Despite higher (P < 0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of plant sterols exert no detrimental effect on erythrocyte fragility.

Topics: Animals; Body Weight; Cricetinae; Erythrocytes; Esters; Fatty Acids; Feeding Behavior; Fish Oils; Lipids; Male; Mesocricetus; Models, Animal; Phytosterols; Weight Gain

This study aimed to investigate whether the combination of plant sterol esters (PSE) with soy protein or soy isoflavones may have extra cholesterol-lowering effects. Male hamsters (n=20/group) were fed diets containing (g/100 g diet) (A) 20 casein (control), (B) 0.24 PSE, (C) 20 intact soy protein (replacing casein), (D) 0.02 soy isoflavones, (E) 0.24 PSE plus 20 soy protein (replacing casein), or (F) 0.24 PSE plus 0.02 soy isoflavones, for 5 wk. All diets contained 0.08 g cholesterol/100 g diet. Compared with the control diet, the PSE and soy protein diets significantly lowered the plasma total cholesterol concentration by 13% (P<0.05) and 9% (P<0.05), respectively, whereas the isoflavone diet (D) had no effect. The combination of PSE and soy protein (diet E) decreased plasma total cholesterol by 26% (P<0.05). The decrease in plasma cholesterol concentration was mainly in the non-HDL fraction. In addition, the combination of PSE and soy protein significantly decreased plasma triacylglycerol concentration (37%, P<0.05) and reduced cholesterol accumulation in the liver. The abundance of hepatic LDL-receptors was not influenced by any of the test diets. PSE selectively increased fecal excretion of neutral sterols by 190% (P<0.05), whereas soy protein increased fecal excretion of neutral sterols and bile acids by 66% (P<0.05) and 130% (P<0.05), respectively. The combination of PSE and soy protein increased the fecal excretion of neutral sterols and bile acids compared with PSE and soy protein alone. In conclusion, the combination of PSE and soy protein more dramatically lowers plasma lipids than the individual ingredients.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cricetinae; Eating; Esters; Feces; Isoflavones; Liver; Male; Organ Size; Phytosterols; Receptors, LDL; Soybean Proteins; Sterols; Triglycerides; Weight Gain

Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids.. Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks.. When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantation significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids.. Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids.

Topics: Anastomosis, Surgical; Animals; Autonomic Denervation; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Feces; Female; Ileum; Intestinal Absorption; Ischemia; Jejunum; Malabsorption Syndromes; Models, Animal; Phytosterols; Reperfusion Injury; Swine; Transplantation, Autologous; Weight Gain

Campesterol is present in all the phytosterol-containing dietary hypocholesterolemic agents in current use. Campesterol is absorbed more efficiently than sitosterol, and the question of its possible atherogenicity has been raised. To test this possibility, rabbits were fed either a semipurified, cholesterol-free diet that has been shown to be atherogenic for this species or the same diet augmented with 0.5 g of phytosterol-rich diet preparations (spreads) containing either sitosterol or sitostanol. The diets contained 295 mg phytosterol per 100 g. After 60 d, serum cholesterol levels in the two phytosterol groups were 78 +/- 4 mg/dL (sitosterol) and 76 +/- 4 mg/dL (sitostanol), respectively. The serum cholesterol level of rabbits fed the control diet was 105 +/- 8 mg/dL. Serum campesterol (microg/mL) levels were higher than sitosterol or sitostanol levels in all groups. Aortic phytosterols were present in nanogram quantities compared to cholesterol, which was present in microgram quantities. The ratio of campesterol/sitosterol/sitostanol in the aortas was: control, 1.00:0.43:0.02; sitosterol, 1:00:0.32:0.01; sitostanol, 1:00:0.34:0.11. Aortic campesterol was present at 4% the concentration of aortic cholesterol, sitosterol at 1.4%, and sitostanol at 0.14%. Aortic lesions were not present in any of the animals.

Topics: Animals; Aorta; Cholesterol; Chromatography, Gas; Diet; Esters; Male; Phytosterols; Rabbits; Sitosterols; Weight Gain

The purpose of this study was to investigate the potential subchronic toxicity of plant sterol esters by a 13-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male and female rats at dose levels of 0, 1000, 3000 and 9000 mg/kg/day for 13 weeks. At the end of treatment period, 10 rats/sex/group were sacrificed, while six rats/sex in the negative control and highest dose groups were sacrificed after a 4-week recovery period. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. Slight decreases in body weight gain were noted at lower doses but were only statistically different from the control animals in the highest dose group. In histopathological examinations, an increase in the incidence of cardiomyopathy with mononuclear cell infiltration was observed in males of the 9000 mg/kg group. Decreased body weight gain and increased incidence of cardiomyopathy observed in the highest dose group were not recovered until the end of the recovery period. There were no adverse effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights in any treatment group. Based on these results, it was concluded that the 13-week repeated oral dose of plant sterol esters resulted in the suppression of body weight gains in both sexes and cardiomyopathy in males at a dose level of 9000 mg/kg/day. The target organ was determined to be heart in males, but not in females. The no-observed-adverse-effect level (NOAEL) was considered to be 3000 mg/kg/day for both sexes.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Drinking; Eating; Esterification; Female; Heart Diseases; Male; Organ Size; Phytosterols; Rats; Rats, Sprague-Dawley; Sex Factors; Weight Gain

4-Desmethylsterols and -stanols reduce plasma total cholesterol (TC) and LDL cholesterol by inhibition of intestinal cholesterol absorption, while the cholesterol-lowering potential of 4,4'-dimethylsterols is less well defined. The present study aimed to compare the effects of 4-desmethylsterols, -stanols, and 4,4'-dimethylsterols on plasma and hepatic cholesterol, sterol excretion and bile acid metabolism. Male golden Syrian hamsters were fed diets containing 13 g/100 g fat, 008 g/100 g cholesterol and 0 (control), 0.24 or 0.48% (w/w) esterified 4-desmethylsterols (sterols) and esterified hydrogenated 4-desmethylsterols (stanols) from common vegetable oils or esterified 4,4'-dimethylsterols from rice bran oil for 5 weeks. Sterol and stanol esters at the dose of 0.24% were equally effective and significantly (P<0.05) lowered TC by 15%, while 0.24% 4,4-dimethylsterols reduced TC by 10%. Liver total and esterified cholesterol concentrations were significantly (P<0.05) lowered by 40, 22, 43 and 31% in hamsters fed 0.48% sterols, 0.24% stanols, 0.48% stanols or 0.48% dimethylsterols, respectively. Daily faecal bile acid excretion and hepatic cholesterol 7alpha-hydroxylase activity were not altered, indicating that sterols, stanols and dimethylsterols had no effect on the intestinal re-absorption of bile acids or on hepatic bile acid synthesis. Daily excretion of cholesterol was significantly higher in hamsters fed esterified sterols and stanols, but was only slightly increased in those fed dimethylsterols. The results indicate that esterified sterols and stanols were equally effective in lowering plasma TC and LDL cholesterol, while dimethylsterol esters caused a weaker cholesterol-lowering effect. Sterols and stanols achieve their cholesterol-lowering effect by stimulating faecal cholesterol excretion through inhibiting intestinal cholesterol absorption, but do not affect bile acid excretion. Other mechanisms need to be considered to explain the effect on plasma and hepatic cholesterol of dimethylsterols.

Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Eating; Feces; Lipids; Lipoproteins; Liver; Male; Mesocricetus; Organ Size; Phytosterols; Weight Gain