Intestinal Lipid Metabolism Research Articles

Tactics of managing a patient with fatty liver disease coursing in the background of a polyorgan digestive tract: clinical observation

Preparations of glycyrrhizic acid (GA) and ursodeoxycholic acid (UDCA) are effective in the treatment of various forms of non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) occurring against the background of duodeno-gastroesophageal reflux. However, their effectiveness in the treatment of hologenic diarrhea and reflux gastritis has not been sufficiently studied. Currently, there are no clinical guidelines for the diagnosis and treatment of patients with hologenic diarrhea and reflux gastritis, including those with obesity and NAFLD. It is assumed that the combined administration of GA and UDCA can be accompanied by a mutual potentiation of the effect of the drugs. The article presents a clinical case of a patient with NAFLD, obesity, dyslipidemia, GERD, refractory to treatment with proton pump inhibitors, associated with duodenogastroesophageal reflux, reflux gastritis and hologenic diarrhea. It was shown that GERD, reflux gastritis, and hologenic diarrhea developed in the long-term period after cholecystectomy. At the same time, the appointment of a complex preparation containing GA (35 mg) and UDCA (250 mg) made it possible to stop the manifestations of a typical reflux syndrome in patients with a form of GERD refractory to proton pump inhibitors, reflux gastritis, and diarrheal syndrome associated with an excess of bile acids, improve lipid profile parameters. It has been shown that the administration of GA (35 mg) and UDCA (250 mg) can improve the parameters of the intestinal microbiome and lipid metabolism, which can be used in the treatment of patients with atherogenic dyslipidemia. At the same time, patients with comorbid pathology, including NAFLD, GERD, reflux esophagitis, hologenic diarrhea, and dyslipidemia require long-term maintenance therapy with GA (35 mg) and UDCA (250 mg).

Chitosan Oligosaccharide Ameliorates Kidney Injury by Improving Intestinal Barrier Dysfunction and Lipid Metabolism in Obese‐insulin Resistant Rats

IntroductionObesity remains a global health problem. High‐fat diet (HFD) consumption increases the risk of type 2 diabetes and initiates kidney injury. Chitosan Oligosaccharide (COS) provides anti‐obesity effects through several mechanisms. However, the effects of COS on preventing obesity‐related kidney injury in obese‐insulin resistance have not been studied. A novel action of COS in activating intestinal tight junction assembly was reported in in vitro via calcium sensing receptor‐mediated AMP‐activated protein kinase (CaSR/AMPK) activation. HFD‐induced gut dysbiosis is related with intestinal barrier dysfunction and systemic low‐grade inflammation. Therefore, AMPK activation might be a therapeutic target for preventing obesity‐related complications. Here, we explored the protective effects of COS in obesity‐induced kidney dysfunction and the involved molecular mechanisms. We hypothesized that COS might exert renoprotection against obesity‐induced kidney injury through increasing intestinal barrier integrity and lipid excretion.MethodsMale Wistar rats were fed with HFD for 16 weeks to induce obesity. Next, HFD rats were randomly divided into 4 groups: HFD, HFD treated with COS 5 or 10 mg/kg/day (COS5 or COS10) and HFD treated with metformin 30 mg/kg/day (MET). The interventions were orally treated for 8 weeks. At the end of experiment, blood, feces, intestinal and renal tissue samples were collected for further investigations.ResultsAfter 16 weeks of high‐fat diet feeding, obesity and glucose intolerance were presented in HFD compared to normal diet (ND) rats, as indicated by the significant increases in body weight (BW), plasma cholesterol and total area under the curve for glucose (TAUCg). Kidney injury were observed at week 24, as shown by elevated kidney injury score and serum creatinine. Treatment with COS5 or COS10 significantly decreased BW, hypercholesterolemia, glucose intolerance and kidney dysfunction. Interestingly, COS10 markedly increased fecal lipid excretion compared with HFD and MET. In addition, intestinal CaSR, p‐AMPK/AMPK and tight junction protein claudin‐1 expressions were downregulated in HFD which were upregulated by COS10 and MET. Renal TNFαR activation and increased proinflammatory cytokines were detected in HFD. Moreover, renal apoptosis markers, Bcl‐2‐associated X protein (Bax) and cleaved caspase‐3, were increased, along with the suppressing of anti‐apoptotic B‐cell lymphoma‐2 (Bcl‐2) in HFD. Treatment with COS10 or MET markedly alleviated renal inflammation and apoptosis.ConclusionCOS exerted renoprotection through attenuating renal inflammation and apoptosis as a result of improving intestinal barrier via CaSR/AMPK activation and lipid absorption in obese rats. Therefore, COS might be an effective new dietary supplement for treating obesity and its related complications in clinical use.

Gut Microbiota and Phenotypic Changes Induced by Ablation of Liver- and Intestinal-Type Fatty Acid-Binding Proteins.

Intestinal fatty acid-binding protein (IFABP; FABP2) and liver fatty acid-binding protein (LFABP; FABP1) are small intracellular lipid-binding proteins. Deficiency of either of these proteins in mice leads to differential changes in intestinal lipid transport and metabolism, and to markedly divergent changes in whole-body energy homeostasis. The gut microbiota has been reported to play a pivotal role in metabolic process in the host and can be affected by host genetic factors. Here, we examined the phenotypes of wild-type (WT), LFABP−/−, and IFABP−/− mice before and after high-fat diet (HFD) feeding and applied 16S rRNA gene V4 sequencing to explore guild-level changes in the gut microbiota and their associations with the phenotypes. The results show that, compared with WT and IFABP−/− mice, LFABP−/− mice gained more weight, had longer intestinal transit time, less fecal output, and more guilds containing bacteria associated with obesity, such as members in family Desulfovibrionaceae. By contrast, IFABP−/− mice gained the least weight, had the shortest intestinal transit time, the most fecal output, and the highest abundance of potentially beneficial guilds such as those including members from Akkermansia, Lactobacillus, and Bifidobacterium. Twelve out of the eighteen genotype-related bacterial guilds were associated with body weight. Interestingly, compared with WT mice, the levels of short-chain fatty acids in feces were significantly higher in LFABP−/− and IFABP−/− mice under both diets. Collectively, these studies show that the ablation of LFABP or IFABP induced marked changes in the gut microbiota, and these were associated with HFD-induced phenotypic changes in these mice.

Eleutheroside E reduces intestinal fat accumulation in Caenorhabditis elegans through neuroendocrine signals.

Acanthopanax senticosus, a small woody shrub of the family Araliaceae, can be used as a functional food with multiple biological activities. Eleutheroside E (EE), an important active component of A. senticosus, has significant effects on neurological diseases. However, whether EE can regulate lipid metabolism has not been reported. The brain can mediate communication between neurons and intestinal cells through long-distance neuroendocrine signals. We speculated that EE might regulate the intestinal lipid metabolism of Caenorhabditis elegans through neuroendocrine signals. First, we found that EE reduced the intestinal fat content of C. elegans, without affecting development, reproduction, food intake or movement. In addition, EE significantly regulated genes and metabolites related to lipid metabolism. EE extensively affected fatty acid synthesis, β-oxidation and lipolysis processes, and regulated the content of various fatty acid and lipid metabolism intermediates. We finally proved that EE reduced intestinal fat storage through serotonin and neuropeptide flp-7-npr-22 pathways in the nervous system. EE is expected to be a functional food that regulates lipid metabolism. © 2022 Society of Chemical Industry.

Effects of Clostridium butyricum Capsules Combined with Rosuvastatin on Intestinal Flora, Lipid Metabolism, Liver Function and Inflammation in NAFLD Patients.

The objective of this study was to investigate the effects of Clostridium butyricum capsules combined with rosuvastatin on the intestinal flora, lipid metabolism, liver function and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). For this purpose, a total of 96 patients with NAFLD were selected as research subjects and randomly divided into a control group (n=48) and an observation group (n=48). The Control group was treated with rosuvastatin, based on which observation group received Clostridium butyricum capsule treatment. The efficacy in the two groups of patients was compared, and the intestinal flora, lipid metabolism, liver function and inflammation were observed. Results showed that the efficacy in the observation group was significantly better than that in the control group (p<0.05). After treatment, the content of Eubacterium rectale in the observation group was lower than that in the control group, while the content of Bacteroides thetaiotaomicron and Bifidobacteria was notably higher than that in the control group (p<0.05). Moreover, the observation group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen III peptide (PIIIP), collagen-IV (C-IV), hyaluronicacid (HA) and laminin (LN) as well as lower levels of tumor necrosis factor-alpha (TNF-α), catabolite activator protein (CAP) and interleukin-6 (IL-6) in serum than the control group (p<0.05). It was concluded that Clostridium butyricum capsules combined with rosuvastatin can effectively improve intestinal flora imbalance, reduce blood lipid levels, and alleviate liver fibrosis and liver function damage in the treatment of NAFLD, so it is of therapeutic value.

The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

Astilbin fromSmilax glabraRoxb. alleviates high-fat diet-induced metabolic dysfunction

Overweight, obesity, and related diseases are currently the major public health problems worldwide. Astilbin, extracted from the rhizome of Smilax glabra Roxb., is known to have significant anti-inflammatory activity and hepatoprotective effect. Studies have shown that it can inhibit adipogenesis in adipocytes in vitro; however, the intervention benefits of astilbin against obesity and related diseases along with its associated mechanisms remain unknown. This study aimed to demonstrate the impact of astilbin consumption on the overall biochemical pattern of high-fat diet (HFD) mice by using a combined multi-omics approach. Our data indicated that astilbin reduced body weight, insulin resistance, and inflammation in mice fed an HFD. Astilbin improved HFD-induced gut microbial dysbiosis by decreasing the Firmicutes-to-Bacteroidetes ratio, by increasing beneficial bacteria such as Alistipes and Muribaculum and decreasing harmful bacteria including Lachnospiraceae FCS020 group, Coriobacteriaceae UCG-002, and Lachnospiraceae UCG-008, resulting in enhanced intestinal carbohydrate and lipid metabolism. Meanwhile, astilbin protected the integrity of the intestinal barrier in HFD mice, increased short-chain fatty acid levels, and reduced metabolic endotoxemia. We further showed that astilbin attenuated hepatic lipid droplet aggregation and triglyceride accumulation in HFD mice, affected glutamate metabolism-related pathways, and enhanced hepatic ATP transduction pathways and attenuated xanthine metabolism pathways in mice, which were positively correlated with the abundance of Alistipes and negatively correlated with Ruminococcaceae UCG-003. The results highlighted that astilbin could be used as a prebiotic for the prevention of "gut-liver axis" damage and metabolic disruption in obese individuals.

Protective effects of taurocholic acid on excessive hepatic lipid accumulation via regulation of bile acid metabolism in grouper.

Dietary bile acid (BA) supplementation can notably ameliorate fatty liver disease caused by high dietary lipids, but the mechanism behind this is poorly understood. The present study was aimed at gaining insight into how TCA (taurocholic acid sodium) reduced hepatic lipid accumulation via the regulation of bile acid metabolism. We explored BA metabolism in juvenile hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). Three trials were: (1) fed the control, high lipid (HD) or gradient TCA diet; (2) fed a BA diet with or without antibiotics; and (3) injected with an agonist or antagonist of TGR5 (G protein-coupled bile acid receptor 1) and FXR (farnesoid X receptor). The results showed that the TCA diet (about 900 mg kg-1) significantly reduced lipid accumulation in the liver, thus improving liver health. The HD suppressed the abundance of bile-salt hydrolase (BSH) microbes, thus decreasing the concentration of unconjugated primary BAs. TCA administration altered the gut microbial composition and weakened the effects of the HD, thus increasing the level of unconjugated BAs. TCA treatment increased the transport and reabsorption of BAs by activating the TGR5 and FXR signaling pathways, and increased the BA pool size. Furthermore, the presence of microbiota in the intestine increased BA reabsorption and the BA pool size. Our study revealed that exogenous TCA alters the structure of intestinal microbiota and BA composition, then activated the FXR expression, thus regulating the BA metabolism via enhanced BA reabsorption. This, in turn, reduced lipid accumulation and improved the health of the liver in grouper.

Fucoidans from Pearsonothuria graeffei prevent obesity by regulating intestinal lipid metabolism and inflammation related signalling pathways.

Background: Fucoidans extracted from sea cucumber Pearsonothuria graeffei (fuc-Pg) are rich in 4-O-sulfation, and have been shown to be potential functional polysaccharides for preventing metabolic syndromes. Objective: The present study was conducted to investigate the effect of fuc-Pg on the prevention of obesity and its underlying mechanism. Method: Mice were fed a normal diet, high-fat diet (HFD), HFD plus low and high dosage of fuc-Pg, and HFD plus simvastatin for 8 weeks. Results: fuc-Pg intervention could significantly decrease weight gain and fat accumulation in the HFD-fed mice. Moreover, fuc-Pg improved serum lipid profile by decreasing serum concentrations of TG, TC, LDL-C, sCD36, ApoB48, and ApoB100 compared with the HFD group. HFD-induced upregulation of intestinal CD36, FABP-1, P-ERK1, and the ratio of p-ERK/ERK was reversed by the fuc-Pg treatment. Moreover, fuc-Pg improved the normal function of white adipose tissue by increasing the expression of UCP1, PPAR-γ, and PGC-1α in the HFD-fed mice. Furthermore, fuc-Pg alleviated systemic inflammation by reducing serum pro-inflammatory factors and breaking the TLR4/NF-κB pathway in both the colon and liver. Conclusion: Fuc-Pg is a potential functional polysaccharide for preventing obesity and systemic inflammation caused by HFD.

A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans.

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.

Microcystin-leucine arginine exposure induced intestinal lipid accumulation and MC-LR efflux disorder in Lithobates catesbeianus tadpoles

Few studies exist on the toxic effects of chronic exposure to microcystins (MCs) on amphibian intestines, and the toxicity mechanisms are unclear. Here, we evaluated the impact of subchronic exposure (30 days) to environmentally realistic microcystin-leucine arginine (MC-LR) concentrations (0 μg/L, 0.5 μg/L and 2 μg/L) on tadpole (Lithobates catesbeianus) intestines by analyzing the histopathological and subcellular microstructural damage, the antioxidative and oxidative enzyme activities, and the transcriptome levels. Histopathological results showed severe damage accompanied by inflammation to the intestinal tissues as the MC-LR exposure concentration increased from 0.5 μg/L to 2 μg/L. RNA-sequencing analysis identified 634 and 1,147 differentially expressed genes (DEGs) after exposure to 0.5 μg/L and 2 μg/L MC-LR, respectively, compared with those of the control group (0 μg/L). Biosynthesis of unsaturated fatty acids and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were upregulated in the intestinal tissues of the exposed groups, with many lipid droplets being observed on transmission electron microscopy, implying that MC-LR may induce lipid accumulation in frog intestines. Moreover, 2 μg/L of MC-LR exposure inhibited the xenobiotic and toxicant biodegradation related to detoxification, implying that the tadpoles’ intestinal detoxification ability was weakened after exposure to 2 μg/L MC-LR, which may aggravate intestinal toxicity. Lipid accumulation and toxin efflux disorder may be caused by MC-LR-induced endoplasmic reticular stress. This study presents new evidence that MC-LR harms amphibians by impairing intestinal lipid metabolism and toxin efflux, providing a theoretical basis for evaluating the health risks of MC-LR to amphibians.

Faecal microbiota transplantation-mediated jejunal microbiota changes halt high-fat diet-induced obesity in mice via retarding intestinal fat absorption.

SummaryFaecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high‐fat diet (HFD)‐induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD‐induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity‐related indicators. Moreover, we found that the anti‐obesity effect of wild boar faecal suspension was associated with jejunal N6‐methyladenosine (m6A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD‐induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6A levels to achieve resistance to obesity.

A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease.

Celiac disease (CeD) is triggered by gluten and results in inflammation and villous atrophy of the small intestine. We aimed to explore the role of miRNA-mediated deregulation of the transcriptome in CeD. Duodenal biopsies of CeD patients (n = 33) and control subjects (n = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (n = 5) and CeD (n = 6). Differential expression analysis was performed to select CeD-associated miRNAs and genes. MiRNA‒target transcript pairs selected from public databases that also displayed a strong negative expression correlation in the current dataset (R < −0.7) were used to construct a CeD miRNA‒target transcript interaction network. The network includes 2030 miRNA‒target transcript interactions, including 423 experimentally validated pairs. Pathway analysis found that interactions are involved in immune-related pathways (e.g., interferon signaling) and metabolic pathways (e.g., lipid metabolism). The network includes 13 genes previously prioritized to be causally deregulated by CeD-associated genomic variants, including STAT1. CeD-associated miRNAs might play a role in promoting inflammation and decreasing lipid metabolism in the small intestine, thereby contributing unbalanced cell turnover in the intestinal crypt. Some CeD-associated miRNAs deregulate genes that are also affected by genomic CeD-risk variants, adding an additional layer of complexity to the deregulated transcriptome in CeD.

Abstract 123: Intestinal Deletion Of 3-hydroxy-3-methylglutaryl-coenzyme A Reductase Promotes Expansion Of The Resident Stem Cell Compartment

While the intestine is the critical interface between cholesterol absorption and excretion, surprisingly little is known about the role of de novo cholesterol synthesis in this organ and how it affects whole body cholesterol homeostasis. The mevalonate pathway is most well-known for the production of cholesterol, but it is also required for the production of essential non-sterol isoprenoids. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, is regulated by a three-protein complex made up of INSIG, SCAP, and SREBP2. Intestine specific knockouts of Scap and Srebp2 both result in severe enteropathy and reduced mouse survival. Here, we assessed the hypothesis that Hmgcr is required for enterocyte viability. Mice harboring floxed alleles for Hmgcr were bred with the Villin-Cre transgene to specifically knock out this enzyme in the villus and crypt epithelial cells of the small intestine (i-KO). The i-KO mice are viable through adulthood and fertile. Hmgcr is efficiently deleted based on analysis via drop digital PCR and qPCR. RNA sequencing shows reduction in all SREBP2 target genes throughout the mevalonate pathway in intestinal epithelial cells. Lipidomics confirms substantial reductions in abundance of all sterol and non-sterol isoprenoids, except 7-dehydrocholesterol and cholesterol. Cholesterol is likely maintained through reabsorption of biliary cholesterol or increased uptake from the circulation. Circulating cholesterol levels and cholesterol absorption are not altered in i-KO mice, but triglyceride absorption is increased through compensatory changes in bile acid composition and intestinal growth. At the cellular level, the intestine rapidly compensates for loss of Hmgcr via dramatic expansion of the stem cell compartment within the crypts. In conclusion, the mechanisms by which the intestine compensates for genetic loss of Hmgcr include altered triglyceride absorption, bile acid composition, increased absorptive surface area, and expansion of the resident stem cell compartment. Together these studies provide insight into the effects of HMGCR knockout in intestinal development and lipid metabolism.

Heritable shifts in redox metabolites during mitochondrial quiescence reprogramme progeny metabolism.

Changes in maternal diet and metabolic defects in mothers can profoundly impact progeny health and disease. However, the biochemical mechanisms that induce the initial reprogramming events at the cellular level have remained largely unknown due to limitations in obtaining pure populations of quiescent oocytes. Here, we show that the precocious onset of Mitochondrial Respiratory Quiescence (MRQ) causes a reprogramming of progeny metabolic state. The premature onset of MRQ drives the lowering of Drosophila oocyte NAD+ levels. NAD+ depletion in the oocyte leads to reduced methionine cycle production of the methyl donor S-adenosylmethionine (SAM) in embryos and lower H3K27-me3 levels, resulting in enhanced levels of progeny intestinal lipid metabolism. In addition, we show that triggering cellular quiescence in mammalian cells and chemotherapy-resistant human cancer cell models induces cellular reprogramming events identical to those seen in Drosophila, suggesting a conserved metabolic mechanism in systems reliant on quiescent cells.

Microecological preparation combined with an modified low-carbon diet improves glucolipid metabolism and cardiovascular complication in obese patients

ObjectiveTo investigate the impact of microecological preparation combined with modified low-carbon diet on the glucolipid metabolism and cardiovascular complication in obese patients.MethodsFrom August 2017 to July 2020, 66 obese patients were recruited, and administrated with an modified low-carbon diet with (group A) or without (Group B) microecology preparation and a balanced diet in control group (group C) for 6 months. Meanwhile, 20 volunteers administrated with a balanced diet were recruited as the healthy control group (group D).ResultsAfter 6-month intervention, obese subjects in group A and B showed significant improvement of body and liver fat mass, reduction of serum lipid levels, intestinal barrier function markers, insulin resistance index (IRI), high blood pressure (HBP) and carotid intima thickness, as compared with subjects in group C. More importantly, subjects in group A had better improvement of vascular endothelial elasticity and intimal thickness than subjects in group B. However, these intervention had no effect on carotid atherosclerotic plaque.ConclusionAdministration of microecological preparation combined with modified low-carbon diet had better improvement of intestinal barrier function, glucose and lipid metabolism, and cardiovascular complications than low-carbon diet in obese patients, but the effect of a simple low-carb diet on carotid atherosclerotic plaque need to be further addressed.

Dietary L-arginine supplementation of tilapia (Oreochromis niloticus) alters the microbial population and activates intestinal fatty acid oxidation.

Currently, little is known about the function of L-arginine in the homeostasis of intestinal lipid metabolism. This study was conducted to test the hypothesis that dietary L-arginine supplementation may alter intestinal microbiota and lipid metabolism in tilapia. Tilapia were fed a basal diet (containing 16.9g L-arginine per kilogram diets) or the basal diet supplemented with 1% or 2% L-arginine for 8 wks. In the present study, we found that dietary supplementation with 1% or 2% L-arginine induced a shift in the community structure of gut microbiota, as showed by increased (p < 0.05) α-diversity, altered (p < 0.05) β-diversity and function profile. This finding coincided with decreased lipid accretion in the intestine of tilapia, which was associated with an enhancement in mRNA levels for peroxisome proliferator-activated receptor α (Pparα), acyl-coenzyme a oxidase 1 (Acox1), and peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α). Using intestinal epithelial cell culture, we demonstrated that the lipid-lowering effect of L-arginine was mainly mediated by activating the AMP-activated protein kinase (AMPK) signaling pathway, carnitine palmitoyltransferase 1 (CPT1), and PPARα, as well as mRNA levels for Acox1 and Acox2. Collectively, our results suggest that dietary L-arginine supplementation of tilapia changed the intestinal microbiota and activated intestinal fatty acid oxidation. However, future studies are warranted to determine the relationship between microbiota and lipid metabolism in the intestine.

Gut Microbiota Modulation In Diabetic Patients

Metabolic disorders and diabetes mellitus are one of the major complex public health problems in the world, and in fact are becoming a global epidemic. It is associated with an increased risk of a large number of complications, including dyslipidemia, cardiovascular disease. The microbiota modulates inflammation, metabolizes indigestible food components, affects intestinal permeability, glucose and lipid metabolism, insulin sensitivity, and overall energy homeostasis. The study investigated the effect of a multistrain probiotic on the intestinal microflora in diabetic patients. As a result of the work carried out, it was shown that the microbiome of patients with diabetes mellitus differs from normal and is depleted in bifidobacteria and some butyrate producers, such as Subdoligranulum, but enriched in Prevotella. The use of a multi-strain probiotic has led to an increase in the biodiversity of the intestinal microflora. Also, in the fecal samples, the content of acetate and butyrate increased, while the concentration of propionate decreased markedly.

Tolerance assessment of dietary bile acids in common carp (Cyprinus carpio L.) fed a high plant protein diet

This study was conducted to investigate the tolerance dose of bile acids as a feed additive in high plant protein (PP) diets of common carp (Cyprinus carpio L.), by evaluating the responses in growth performance, hepatopancreas and intestinal histology, and glucose and lipid metabolism regulation. Three isonitrogenous and isoenergetic diets (36% PP and 10% fish meal) were prepared with bile acids supplementation of 0 (B0), 60 (B60), and 600 (B600) mg/kg, in which B600 was assayed as 10-fold the maximum recommended level (60 mg/kg) obtained by a previous efficacy test. Each diet was fed to six replicates of 30 common carps (initial body weight = 13.7 ± 0.01 g). Bile acids supplementation decreased feed conversion rate, hepatopancreas-somatic index, and hepatopancreas lipid content significantly. Dietary bile acids improved histopathological symptoms induced by the high PP diet, accompanied with down-regulated inflammatory responses (tnfα, il1β, il10, and tgfβ1) in distal intestine; and up-regulated anti-inflammatory cytokines (il10), but reduced apoptosis response (cleaved caspase3, detected by immunofluorescence staining) in the hepatopancreas. The ameliorated pathological symptoms and liver function in the B60 and B600 groups were closely related to the improved glucose metabolism regulation, with decreased fasting blood glucose and increased gluconeogenesis enzyme activity (G6Pase). Simultaneously, improved lipid metabolism was observed with up-regulated lipolysis (atgl) and bile acids synthesis (cyp7a1 and cyp8b1), but down-regulated cholesterol synthesis (hmgcr) gene-related mRNA, together with enhanced cholesterol transportation and bile acid recirculation to reduce lipid accumulation in the hepatopancreas. The phosphorylation of ERK1/2 was positively regulated by the systematic recovery of metabolic liver disease induced by the high PP diet. In conclusion, addition of 60 mg/kg bile acids is effective in common carp, with a 10-fold safety margin in commercial feed.

Investigating the Role Intestinal-Specific FXR and SHP in Regulating Lipid Metabolism in Mice

Dysregulation of lipid metabolism is a causal factor that can lead to a variety of disorders, such as obesity and metabolic syndrome. Dietary fats are digested in the small intestine by the physiological detergents known as bile acids. They emulsify the fats and break them down into smaller molecules in order for the enterocytes to absorb the nutrients through simple diffusion or through the utilization of specific lipid transporters. Interestingly, the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) not only regulates bile acid synthesis and circulation, but also lipid metabolism. Although many studies have examined the role of FXR in hepatic and intestinal lipid metabolism, studies investigating the role of SHP in the intestine are still lacking. Although FXR and SHP cooperate to regulate many metabolic pathways, FXR or SHP knockout models exhibit different lipid phenotypes. These data indicate there are FXR-dependent and -independent pathways of SHP that controls lipid metabolism. To delineate these two interconnecting yet separate pathways, we will utilize intestine-specific Shp knockout (IShpKO) and intestine-specific Fxr knockout (IFxrKO) mice model and place them on high fat diet to investigate their intestinal intestinal absorption and transportation of lipids. We will also monitor the bile acid pool in the intestine, serum, and liver in these knockouts to evaluate the consequence of intestinal deletion of Fxr as well as Shp on bile acid homeostasis and how this may affect lipid absorption. These experiments will identify how FXR and/or SHP regulates intestinal fat digestion and absorption and if this is secondary to the alterations in bile acid concentration and lipid transporters. In addition, we will also investigate the intestinal Fxr-Shp double knockout (IDKO) mice model to determine their combined contribution in intestinal lipid metabolism. Overall, the results obtained from this research will elucidate if intestinal FXR and SHP cooperate or can independently regulate lipid metabolism and homeostasis.