Fecal Fatty Acid Excretion Research Articles

Protocatechuic acid alleviates TMAO-aggravated atherosclerosis via mitigating inflammation, regulating lipid metabolism, and reshaping gut microbiota.

Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. As a natural phenolic acid, protocatechuic acid (PCA) is abundant in various plant foods. The present study investigated the effect of PCA on TMAO-aggravated atherosclerosis in ApoE-/- mice. The mice were randomly divided into five groups and fed one of the following five diets for 12 weeks: namely a low-fat diet (LFD), a western diet (WD), a WD + 0.2% TMAO diet (WDT), a WDT + 0.5% PCA diet (WDT + LPCA), and a WDT + 1.0% PCA diet (WDT + HPCA). Results demonstrated that dietary TMAO exacerbated the development of atherosclerosis by eliciting inflammation and disturbing lipid metabolism. The diet with PCA at 1% reduced TMAO-induced aortic plaque by 30% and decreased the levels of plasma pro-inflammatory cytokines. PCA also improved lipid metabolism by up-regulating the hepatic gene expression of peroxisome proliferator-activated receptor alpha (PPARα). In addition, PCA supplementation enhanced fecal excretion of fatty acids and decreased hepatic fat accumulation. PCA supplementation favorably modulated gut microbiota by increasing the α-diversity with an increase in the abundance of beneficial genera (Rikenella, Turicibacter, Clostridium_sensu_stricto and Bifidobacterium) and a decrease in the abundance of the harmful Helicobacter genus. In summary, PCA could alleviate the TMAO-exacerbated atherosclerosis and inflammation, improve the lipid metabolism, and modulate gut microbiota.

Dietary Bamboo Charcoal Decreased Visceral Adipose Tissue Weight by Enhancing Fecal Lipid Excretions in Mice with High-Fat Diet-Induced Obesity.

Bamboo charcoal (BC) powder is prepared from thick bamboo stems via dry distillation and is often used for food coloring. Due to the unique structure of the micropores in bamboo stems, BC powder also serves as an indigestible carrier to prevent the absorption of toxic substances and nutrients from the digestive tract. This study evaluated the health-promoting function of BC, particularly its effects in decreasing visceral adipose tissue in a mouse model with high-fat diet (HFD)-induced obesity. Four-week-old male C57BL/6J mice were divided into three groups and fed either a low-fat (LF) diet (7% fat), HF diet (25% fat), or HF diet with 0.5% BC (HF-BC). After 80 days, the HF-BC diet was found to have decreased epididymal and mesenteric white adipose tissue weights compared to HFD. The inhibition of visceral fat accumulation by BC intake was partly due to enhanced fecal fatty acid excretion induced by its bile acid-binding and pancreatic lipase inhibition. Contrarily, the gut microbiota, known to influence systemic energy metabolism, did not change significantly between the HF and HF-BC groups. These results indicate that dietary BC inhibits visceral fat accumulation, which could reduce obesity development.

The Positional Distribution of Fatty Acids in Palm Oil and Lard Influences Their Biologic Effects in Rats

Dietary fatty acids in the sn-2 position are preferentially absorbed as monoacylglycerols. To determine whether they also have more important biologic effects, rats were fed for 2 and 4 mo a purified diet containing native palm oil, interesterified palm oil, native lard or interesterified lard. Interesterification that increased or decreased the level of fatty acids in position 2 depending on the fat, resulted in significant corresponding changes in the fecal excretion of saturated fatty acids. Fecal excretion of saturated fatty acids was associated with significant changes in some plasma fatty acids. Interesterification in lard resulted in significantly lower plasma triglycerides, and in palm oil, increased platelet aggregation induced by ADP. Lipemia, platelet aggregation and associated plasma fatty acids (palmitic, heneicosanoic and docosahexaenoic acids) were significantly affected only by dietary fatty acids at the sn-2 position. Even without changes in absorption, only linoleic acid in position 2 was correlated with the plasma concentration of the corresponding longer chain arachidonic acid. These results in rats confirm that the fatty acids (saturated and unsaturated) in position 2 of dietary triglycerides play a crucial role in the metabolism and biologic effects of these fatty acids.

Short-Term Dietary Calcium Fortification Increases Fecal Saturated Fat Content and Reduces Serum Lipids in Men

The effect of dietary calcium on fecal fatty acid excretion and serum lipids was tested in a randomized, single-blind metabolic study in 13 healthy men with moderate hypercholesterolemia. A low calcium base diet containing 34% of energy from fat, 13% from saturated fatty acids, 240 mg cholesterol/d and 410 mg Ca/d was compared with a fortified version in which calcium citrate malate was added to orange juice, (550 mg) muffins (750 mg), and two tablets (500 mg) for a total calcium intake of 2200 mg/d. Fecal collections (72 h, d 8, 9, 10) and blood from fasting subjects for lipids and lipoproteins (d 9, 10, 11) were obtained. The percentage of dietary saturated fat excreted per day increased from 6 to 13% with calcium fortification. There was no change in fecal bile acid excretion. The high Ca diet significantly reduced total cholesterol 6% (5.99 to 5.66 mmol/L), LDL cholesterol 11% (4.13 to 3.67 mmol/L), and apolipoprotein B concentrations 7% when compared with the low Ca diet (P < 0.05). There was no change in HDL cholesterol or apolipoprotein A1 concentrations. Urinary calcium excretion increased from 146 to 230 mg/d when the high Ca diet was consumed. Calcium fortification was effective in lowering total and LDL cholesterol concentrations and may be an effective adjunct to cholesterol-lowering diet therapy.

A Systems Analysis of Phenotype Heterogeneity in APOE*3Leiden.CETP Mice Induced by Long-Term High-Fat High-Cholesterol Diet Feeding.

Within the human population, considerable variability exists between individuals in their susceptibility to develop obesity and dyslipidemia. In humans, this is thought to be caused by both genetic and environmental variation. APOE*3-Leiden.CETP mice, as part of an inbred mouse model in which mice develop the metabolic syndrome upon being fed a high-fat high-cholesterol diet, show large inter-individual variation in the parameters of the metabolic syndrome, despite a lack of genetic and environmental variation. In the present study, we set out to resolve what mechanisms could underlie this variation. We used measurements of glucose and lipid metabolism from a six-month longitudinal study on the development of the metabolic syndrome. Mice were classified as mice with either high plasma triglyceride (responders) or low plasma triglyceride (non-responders) at the baseline. Subsequently, we fitted the data to a dynamic computational model of whole-body glucose and lipid metabolism (MINGLeD) by making use of a hybrid modelling method called Adaptations in Parameter Trajectories (ADAPT). ADAPT integrates longitudinal data, and predicts how the parameters of the model must change through time in order to comply with the data and model constraints. To explain the phenotypic variation in plasma triglycerides, the ADAPT analysis suggested a decreased cholesterol absorption, higher energy expenditure and increased fecal fatty acid excretion in non-responders. While decreased cholesterol absorption and higher energy expenditure could not be confirmed, the experimental validation demonstrated that the non-responders were indeed characterized by increased fecal fatty acid excretion. Furthermore, the amount of fatty acids excreted strongly correlated with bile acid excretion, in particular deoxycholate. Since bile acids play an important role in the solubilization of lipids in the intestine, these results suggest that variation in bile acid homeostasis may in part drive the phenotypic variation in the APOE*3-Leiden.CETP mice.

Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr-/-.Leiden mice with manifest obesity-associated NASH.

Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however, it remains unclear whether individual BCAAs can attenuate already established NASH and associated oxidative-inflammatory stress. After a 26 weeks run-in on fast food diet (FFD), obese Ldlr-/-.Leiden mice were treated for another 12 weeks with either valine or isoleucine (3% of FFD) and then compared to FFD controls. Valine and isoleucine did not affect obesity, dyslipidemia, gut permeability, or fecal fatty acid excretion, but significantly reduced hyperinsulinemia. Valine and isoleucine reduced ALT, CK18-M30, and liver steatosis with a particularly pronounced suppression of the microvesicular component (-61% by valine and -71% by isoleucine). Both BCAAs decreased intrahepatic diacylglycerols and 4-hydroxynonenal immunoreactivity, a marker for oxidative stress-induced lipid peroxidation. Functional genomics analysis demonstrated that valine and isoleucine affected BCAA metabolism genes, deactivated master regulators of anabolic pathways related to steatosis (e.g., SREBPF1), and activated master regulators of mitochondrial biogenesis (e.g., PPARGC1A) and lipid catabolism (e.g., ACOX1, AMPK). This correction of critical metabolic pathways on gene expression level was accompanied by a significant decrease in histological liver inflammation, and suppression of FFD-stimulated cytokine and chemokine proteins KC/CXCL1, MCP-1/CCL2, and MIP-2/CXCL2 and their pathways. In conclusion, dietary intervention with either valine or isoleucine corrected liver diacylglycerols, gene expression of multiple metabolic processes, and reduced NASH histology with profound hepatoprotective effects on oxidative stress and inflammatory proteins.

Induction of fecal cholesterol excretion is not effective for the treatment of hyperbilirubinemia in Gunn rats.

Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. To determine whether increasing fecal cholesterol excretion could ameliorate unconjugated hyperbilirubinemia, we treated hyperbilirubinemic Gunn rats with ezetimibe (EZE), an intestinal cholesterol absorption inhibitor, and/or a liver X receptor (LXR) and farnesoid X receptor (FXR) agonist (T0901317 (T09) and obeticholic acid (OCA), respectively), known to stimulate TICE. We found that EZE treatment alone or in combination with T09 or OCA increased fecal cholesterol disposal but did not lower plasma UCB levels. These findings do not support a link between the regulation of transintestinal excretion of cholesterol and bilirubin. Furthermore, induction of fecal cholesterol excretion is not a potential therapy for unconjugated hyperbilirubinemia. Increasing fecal cholesterol excretion is not effective to treat unconjugated hyperbilirubinemia. This is the first time a potential relation between transintestinal excretion of cholesterol and unconjugated bilirubin is investigated. Transintestinal excretion of cholesterol and unconjugated bilirubin do not seem to be quantitatively linked. Unlike intestinal fatty acids, cholesterol cannot "capture" unconjugated bilirubin to increase its excretion. These results add to our understanding of ways to improve and factors regulating unconjugated bilirubin disposal in hyperbilirubinemic conditions.

Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child.

Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children. Prospective multicenter cohort study. Three U.K.-based PICUs. Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037). Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.

Effect of dietary protein level and conjugated linoleic acid supply on milk secretion and fecal excretion of fatty acids

Little is known about the influence of dietary crude protein (CP) restriction and rumen-protected conjugated linoleic acid (rpCLA) supply on digestibility and metabolism of nutrients in dairy cows. This study investigated the effect of low dietary CP level combined with rpCLA supply on FA secretion into milk and excretion via feces in dairy cows. Twenty Friesian cows were involved in a 4 × 4 Latin square design over 3-week periods. Cows were fed 4 different rations based on 2 dietary CP levels (150 and 123 g/kg dry matter of CP), each one with or without the addition of a 80 g/d supplement of rpCLA. Feed, feces and milk samples were analyzed for their fatty acid content (FA) and data were used to calculate apparent FA transfer as the ratios between the daily FA secretion in milk, or excretion in feces, and intake. Dietary CP restriction had little influence on apparent FA transfer from the feed to the feces and the milk, but slightly increased the apparent transfer to the milk of 14:0iso (P = 0.031) and 15:0iso (P = 0.006), and tended to increase transfer of other branched FAs of microbial origin, i.e. 15:0anteiso (P = 0.06), 16:0iso (P = 0.06) and 17:0iso (P = 0.07). The rpCLA supply lowered the secretion/intake ratio of total FAs in the milk (P = 0.02), particularly those with the shortest chains and with even numbers of carbons, but had no effect on apparent transfer of branched and odd FAs of microbial origin. The rpCLA supply greatly reduced (P < 0.001) the secretion/intake ratio of 18:2c9,t11 and 18:2t10,c12 in the milk but also increased (P < 0.001) the milk secretion of 18:2c11,t13 (not supplied with the rpCLA) leaving no trace of it in the feces. In conclusion, the CP × rpCLA interaction had negligible effects of FA profile of both milk and feces. Our results suggested that rpCLA supply alters milk FA profile, mainly reducing the de novo synthesis of short-chain FAs and the Δ9 desaturase activity in the bovine mammary gland. Little influence of the dietary CP on animal digestive and metabolic processing of nutrients at the levels used in this experiment were suggested by small variations in the transfer of FA from feed to milk and feed to feces.

Rare sugars, d-allulose, d-tagatose and d-sorbose, differently modulate lipid metabolism in rats.

Rare sugars including d-allulose, d-tagatose, and d-sorbose are present in limited quantities in nature; some of these rare sugars are now commercially produced using microbial enzymes. Apart from the anti-obesity and anti-hyperglycaemic activities of d-allulose, effects of these sugars on lipid metabolism have not been investigated. Therefore, we aimed to determine if and how d-tagatose and d-sorbose modulate lipid metabolism in rats. After feeding these rare sugars to rats, parameters on lipid metabolism were determined. No diet-related effects were observed on body weight and food intake. Hepatic lipogenic enzyme activity was lowered by d-allulose and d-sorbose but increased by d-tagatose. Faecal fatty acid excretion was non-significantly decreased by d-allulose, but significantly increased by d-sorbose without affecting faecal steroid excretion. A trend toward reduced adipose tissue weight was observed in groups fed rare sugars. Serum adiponectin levels were decreased by d-sorbose relative to the control. Gene expression of cholesterol metabolism-related liver proteins tended to be down-regulated by d-allulose and d-sorbose but not by d-tagatose. In the small intestine, SR-B1 mRNA expression was suppressed by d-sorbose. Lipid metabolism in rats varies with rare sugars. Application of rare sugars to functional foods for healthy body weight maintenance requires further studies. © 2017 Society of Chemical Industry.

Mice abundant in muricholic bile acids show resistance to dietary induced steatosis, weight gain, and to impaired glucose metabolism

High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/-) and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet. Food intake and body and liver weights were determined, and lipids in liver, serum and feces were measured. Further, responses during oral glucose and intraperitoneal insulin tolerance tests were evaluated. On the high fat diet, Cyp8b1-/- mice displayed less weight gain compared to wildtype littermates (Cyp8b1+/+). In addition, liver enlargement with steatosis and increases in serum LDL-cholesterol were strongly attenuated in Cyp8b1-/- mice on high fat diet. Fecal excretion of cholesterol was increased and there was a strong trend for doubled fecal excretion of free fatty acids, while excretion of triglycerides was unaltered, indicating dampened lipid absorption. On high fat diet, Cyp8b1-/- mice also presented lower serum glucose levels in response to oral glucose gavage or to intraperitoneal insulin injection compared to Cyp8b1+/+. In conclusion, following exposure to a high fat diet, Cyp8b1-/- mice are more resistant against weight gain, steatosis, and to glucose intolerance than Cyp8b1+/+ mice. Reduced lipid absorption may in part explain these findings. Overall, the results suggest that muricholic bile acids may be beneficial against the metabolic syndrome.

Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders

Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice in a mixed B6/129Sv genetic background to C57BL/6J mice to generate Cyp7a1(-/-) mice in a near-pure C57BL/6J background. These mice survive well and have normal growth and a bile acid pool size ∼60% of WT mice. The expression of the genes in the alternative bile acid synthesis pathway are upregulated, resulting in a more hydrophilic bile acid composition with reduced cholic acid (CA). Surprisingly, Cyp7a1(-/-) mice have improved glucose sensitivity with reduced liver triglycerides and fecal bile acid excretion, but increased fecal fatty acid excretion and respiratory exchange ratio (RER) when fed a high-fat/high-cholesterol diet. Supplementing chow and Western diets with CA restored bile acid composition, reversed the glucose tolerant phenotype, and reduced the RER. Our current study points to a critical role of bile acid composition, rather than bile acid pool size, in regulation of glucose, lipid, and energy metabolism to improve glucose and insulin tolerance, maintain metabolic homeostasis, and prevent high-fat diet-induced metabolic disorders.

Mice Abundant in Muricholic Bile Acids Show Resistance to Dietary Induced Steatosis, Weight Gain, and to Impaired Glucose Metabolism.

High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/-) and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet. Food intake and body and liver weights were determined, and lipids in liver, serum and feces were measured. Further, responses during oral glucose and intraperitoneal insulin tolerance tests were evaluated.On the high fat diet, Cyp8b1-/- mice displayed less weight gain compared to wildtype littermates (Cyp8b1+/+). In addition, liver enlargement with steatosis and increases in serum LDL-cholesterol were strongly attenuated in Cyp8b1-/- mice on high fat diet. Fecal excretion of cholesterol was increased and there was a strong trend for doubled fecal excretion of free fatty acids, while excretion of triglycerides was unaltered, indicating dampened lipid absorption. On high fat diet, Cyp8b1-/- mice also presented lower serum glucose levels in response to oral glucose gavage or to intraperitoneal insulin injection compared to Cyp8b1+/+.In conclusion, following exposure to a high fat diet, Cyp8b1-/- mice are more resistant against weight gain, steatosis, and to glucose intolerance than Cyp8b1+/+ mice. Reduced lipid absorption may in part explain these findings. Overall, the results suggest that muricholic bile acids may be beneficial against the metabolic syndrome.

VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. The Vegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism.

Dietary ε-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis.

Effects of Porcine Hemoglobin on Serum Lipid Content and Fecal Lipid Excretion in Rats

The purpose of this study was to elucidate the effects of dietary hemoglobin on serum and liver lipid contents in rats, and the ability of hemoglobin hydrolysates to disrupt lipid absorption. After rats had been fed on casein- or porcine hemoglobin-containing diets for 4 weeks, their serum and liver lipid contents and fecal cholesterol, bile acid, and nitrogen excretion were measured. To elucidate the mechanism of lipid absorption by dietary hemoglobin, we also examined lipase activity, micellar solubility of cholesterol, and bile acid binding activity in the presence of hemoglobin hydrolysates. Dietary hemoglobin decreased serum and liver triglyceride and cholesterol contents and increased fecal fatty acid, cholesterol, and bile acid excretion. In addition, hemoglobin hydrolysates inhibited lipase activity compared with casein hydrolysates in an in vitro study. These results suggested that the hypolipidemic effect of hemoglobin is mediated by increased fecal lipid excretion, and that decreased lipase activity by hemoglobin is at least partially responsible for this result. The observed effects were documented with an 8 g/kg hemoglobin diet, which is lower than in other studies; therefore. hemoglobin may be useful in the prevention of lifestyle-related diseases.

Dietary Hydroxypropyl Methylcellulose Increases Excretion of Saturated and Trans Fats by Hamsters Fed Fast Food Diets

In animal studies, hydroxypropyl methylcellulose (HPMC) intake results in increased fecal fat excretion; however, the effects on dietary saturated fatty acids (SATs) and trans-fatty acids (TRANS) remain unknown. This study investigated the effect of HPMC on digestion and absorption of lipids in male Golden Syrian hamsters fed either freeze-dried ground pizza (PZ), pound cake (PC), or hamburger and fries (BF) supplemented with dietary fiber from either HPMC or microcrystalline cellulose (MCC) for 3 weeks. We observed greater excretion of SATs and TRANS by both diets supplemented with HPMC or MCC as compared to the feed. SAT, TRANS, and unsaturated fatty acids (UNSAT) contents of feces of the PZ diet supplemented with HPMC were 5-8 times higher than diets supplemented with MCC and tended to be higher in the PC- and BF-HPMC supplemented diets as well. We also observed significant increases in fecal excretion of bile acids (2.6-3-fold; P < 0.05), sterols (1.1-1.5-fold; P < 0.05), and unsaturated fatty acids (UNSAT, 1.7-4.5-fold; P < 0.05). The animal body weight gain was inversely correlated with the excretion of fecal lipid concentrations of bile acids (r = -0.56; P < 0.005), sterols (r = -0.48; P < 0.005), SAT (r = -0.69; P < 0.005), UNSAT (r = -0.67; P < 0.005), and TRANS (r = -0.62; P < 0.005). Therefore, HPMC may be facilitating fat excretion in a biased manner with preferential fecal excretion of both TRANS and SAT in hamsters fed fast food diets.

Grape extract and α-Tocopherol effect in cardiovascular disease model of Apo E -/- Mice

To verify the effect of consumption of grape extract isolated or combined with α-tocopherol supplementation on atherosclerosis model with Apo E -/- mice. After six weeks of atherogenic diet, Apo E -/- mice were divided into the following groups: Control, Grape, Tocopherol and Grape plus Tocopherol. The treatment progressed for 11 weeks when animals were submitted to euthanasia. All the treatments presented hypocholesterolemic effect with reduction of serum and liver cholesterol levels. This effect was parallel to an increase in the fecal excretion of cholesterol. There was also a higher fecal excretion of saturated fatty acids in groups receiving grape extract or α-tocopherol. All the groups treated presented a tendency to show higher levels of vitamin E. The fatty acid profile showed a tendency for monounsaturated fatty acid preservation after grape extract and α-tocopherol consumption. Morphological analysis revealed a lower degree of evolution of the atherosclerotic plaque of the animals that were fed α-tocopherol combined with grape extract, even when no difference was found in the size of the largest lesion. A synergistic effect between the polyphenols and α-tocopherol was observed, resulting in diminished evolution of atherosclerosis and a greater beneficial effect on atherosclerosis than the isolated consumption of antioxidants.

Production and bioavailability of calcium and magnesium salts of omega-3 fatty acids

In order to provide an alternative to traditional liquid fish oil gelatin capsules, we developed a solid, powdered form of omega-3 fish oil concentrate by forming calcium- and magnesium-fatty acid salts. These salts were produced using a concentrated fish oil ethyl ester that contained in excess of 60% omega-3 fatty acids. The bioavailability of these omega-3 salts was compared with that of fish oil ethyl ester in mice. Animals were given 8 mg of omega-3 fatty acid ethyl ester concentrate (control), calcium- or magnesium-omega-3 salts daily for three weeks. The omega-3 salt products resulted in omega-3 fatty acid content in serum and red blood cell membranes comparable to that produced by the ethyl ester supplementation. In addition, fecal excretion of omega-3 fatty acids was not increased by the presence of calcium or magnesium. In fact, there was a tendency for less omega-3 fatty acids to be excreted.

Metabonomic and Microbiological Analysis of the Dynamic Effect of Vancomycin-Induced Gut Microbiota Modification in the Mouse

The effects of the antibiotic vancomycin (2 x 100 mg/kg/day) on the gut microbiota of female mice (outbred NMRI strain) were studied, in order to assess the relative contribution of the gut microbiome to host metabolism. The host's metabolic phenotype was characterized using (1)H NMR spectroscopy of urine and fecal extract samples. Time-course changes in the gut microbiotal community after administration of vancomycin were monitored using 16S rRNA gene PCR and denaturing gradient gel electrophoresis (PCR-DGGE) analysis and showed a strong effect on several species, mostly within the Firmicutes. Vancomycin treatment was associated with fecal excretion of uracil, amino acids and short chain fatty acids (SCFAs), highlighting the contribution of the gut microbiota to the production and metabolism of these dietary compounds. Clear differences in gut microbial communities between control and antibiotic-treated mice were observed in the current study. Reduced urinary excretion of gut microbial co-metabolites phenylacetylglycine and hippurate was also observed. Regression of urinary hippurate and phenylacetylglycine concentrations against the fecal metabolite profile showed a strong association between these urinary metabolites and a wide range of fecal metabolites, including amino acids and SCFAs. Fecal choline was inversely correlated with urinary hippurate. Metabolic profiling, coupled with the metagenomic study of this antibiotic model, illustrates the close inter-relationship between the host and microbial "metabotypes", and will provide a basis for further experiments probing the understanding of the microbial-mammalian metabolic axis.