Enhancing bile tolerance of Lactobacilli is involved in the hypolipidemic effects of liraglutide

2021 ◽  
Author(s):  
Chang Wang ◽  
Hai-Jie Hu ◽  
Qing-Qing Dong ◽  
Rui Huang ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Normal Saline ◽  
Intestinal Flora ◽  
Ldl Receptor ◽  
Basal Diet ◽  
Lipid Lowering ◽  
Bile Tolerance ◽  
Glycolipid Metabolism ◽  
Real Time Quantitative Pcr ◽  
Rdna Sequencing ◽  
Key Enzyme

Abstract Liraglutide is an analogue of human glucagon-like peptide-1 (GLP-1), an endogenous intestinal hormone which play essential roles in the regulation of glycolipid metabolism. To investigate the role of lactic acid bacteria (LAB) in the lipid-lowering effect of liraglutide, forty mice were divided into normal saline-treated basal diet (NFD), normal saline-treated high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 μg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. 16S rDNA sequencing, real-time quantitative PCR and western blot were used to detected changes of intestinal flora, cholesterol 7α-hydroxylase (CYP7A1), LDL-receptor (LDLR) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Results showed that liraglutide could up-regulate CYP7A1 and LDLR, whereas down-regulate HMGCR. Besides, liraglutide enhance the abundance of lactobacillaceae in gut of hyperlipidemic mice and increase the bile tolerance ability of LAB by up-regulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly down-regulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and threw a light on research and development of anti-obesity, hypolipidemic and cholesterol-lowering drugs or functional foods.

scholarly journals Anti-aging Effect of Agar Oligosaccharide on Male Drosophila melanogaster and its Preliminary Mechanism

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 632 ◽  
Author(s):  
Ma ◽  
Yang ◽  
Wang ◽  
Dai
Keyword(s):  
Drosophila Melanogaster ◽  
Intestinal Flora ◽  
Aging Effect ◽  
Basal Diet ◽  
Nutritional Supplement ◽  
Intestinal Immunity ◽  
Rdna Sequencing ◽  
Immunity Genes ◽  
Mda Content ◽  
Different Doses

Agar oligosaccharide (AOS) is a marine prebiotic with apparent anti-inflammatory, antioxidant and anti-tumor effects. During this study, different doses of AOS are added to a basal diet to evaluate its effects on the lifespan, motor vigor and reproduction of male Drosophila melanogaster. Additionally, the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase (CAT) and the malondialdehyde (MDA) content in male Drosophila are examined on the 10th, 25th and 40th days. The fly midguts are removed on the 10th and 40th days for analyses of the intestinal microbial community by 16S rDNA sequencing and the expression level of intestinal immunity genes by quantitative real-time PCR (RT-PCR). The results show that AOS significantly prolonged the average and maximum lifespan and increased the antioxidant capacity of male Drosophila. Additionally, AOS significantly regulated the structure of the intestinal flora of "old" flies (40 days) and upregulated the expression of immune deficiency (IMD) genes to improve the intestinal immunity, which could be beneficial for delaying aging in old flies. The above-described results provide a theoretical basis for the application of AOS, a type of marine oligosaccharide, as a nutritional supplement or immunomodulator.

Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis

2019 ◽  
Vol 20 (10) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Novel Target ◽  
New Treatments ◽  
And Function

Background:One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.Methods:We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.Results:New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.Conclusion:PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.

scholarly journals Genetics of Hypercholesterolemia: Comparison Between Familial Hypercholesterolemia and Hypercholesterolemia Nonrelated to LDL Receptor

2020 ◽  
Vol 11 ◽  
Author(s):  
Estíbaliz Jarauta ◽  
Ana Ma Bea-Sanz ◽  
Victoria Marco-Benedi ◽  
Itziar Lamiquiz-Moneo
Keyword(s):  
Cardiovascular Risk ◽  
Familial Hypercholesterolemia ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Ldl Receptor ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Single Nucleotide Variants ◽  
Cascade Screening ◽  
The Moment

Severe hypercholesterolemia (HC) is defined as an elevation of total cholesterol (TC) due to the increase in LDL cholesterol (LDL-C) >95th percentile or 190 mg/dl. The high values of LDL-C, especially when it is maintained over time, is considered a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), mostly expressed as ischemic heart disease (IHD). One of the best characterized forms of severe HC, familial hypercholesterolemia (FH), is caused by the presence of a major variant in one gene (LDLR, APOB, PCSK9, or ApoE), with an autosomal codominant pattern of inheritance, causing an extreme elevation of LDL-C and early IHD. Nevertheless, an important proportion of serious HC cases, denominated polygenic hypercholesterolemia (PH), may be attributed to the small additive effect of a number of single nucleotide variants (SNVs), located along the whole genome. The diagnosis, prevalence, and cardiovascular risk associated with PH has not been fully established at the moment. Cascade screening to detect a specific genetic defect is advised in all first- and second-degree relatives of subjects with FH. Conversely, in the rest of cases of HC, it is only advised to screen high values of LDL-C in first-degree relatives since there is not a consensus for the genetic diagnosis of PH. FH is associated with the highest cardiovascular risk, followed by PH and other forms of HC. Early detection and initiation of high-intensity lipid-lowering treatment is proposed in all subjects with severe HC for the primary prevention of ASCVD, with an objective of LDL-C <100 mg/dl or a decrease of at least 50%. A more aggressive reduction in LDL-C is necessary in HC subjects who associate personal history of ASCVD or other cardiovascular risk factors.

scholarly journals Dietary Recombinant Phycoerythrin Modulates the Gut Microbiota of H22 Tumor-Bearing Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 665 ◽  
Author(s):  
Hongtao Qi ◽  
Ying Liu ◽  
Xin Qi ◽  
Hui Liang ◽  
Huaxin Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Intestinal Flora ◽  
Endocrine Function ◽  
Intragastric Administration ◽  
Beneficial Bacteria ◽  
Tumor Bearing ◽  
Immune System Development ◽  
Rdna Sequencing ◽  
Intestinal Immune System

Normal intestinal flora is widely involved in many functions of the host: nutritional metabolism; maintenance of intestinal microecological balance; regulation of intestinal endocrine function and nerve signal transduction; promotion of intestinal immune system development and maturation; inhibition of pathogenic bacteria growth and colonization, reduction of its invasion to intestinal mucosa, and so on. In recent years, more and more studies have shown that intestinal flora is closely related to the occurrence, development, and treatment of various tumors. It is indicated that recombinant phycoerythrin (RPE) has significant anti-tumor and immunomodulatory effects. However, little is known about the mechanism of the effect of oral (or intragastric) administration of RPE on gut microbiota in tumor-bearing animals. In this study, using high-throughput 16S rDNA sequencing, we examined the response of gut microbiota in H22-bearing mice to dietary RPE supplementation. The results showed that the abundance of beneficial bacteria in the mice intestinal flora decreased and that of the detrimental flora increased after inoculation with tumor cells (H22); following treatment with dietary RPE, the abundance of beneficial bacteria in the intestinal flora significantly increased and that of detrimental bacteria decreased. In this study, for the first time, it was demonstrated that dietary RPE could modulate the gut microbiota of the H22 bearing mice by increasing the abundance of beneficial bacteria and decreasing that of detrimental bacteria among intestinal bacteria, providing evidence for the mechanism by which bioactive proteins affect intestinal nutrition and disease resistance in animals.

scholarly journals High-throughput sequencing analysis of intestinal flora changes in ESRD and CKD patients

2019 ◽  
Author(s):  
Jianguang Hu ◽  
Xiaoshi Zhong ◽  
Jing Yan ◽  
Daoyuan Zhou ◽  
Danping Qin ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Throughput Sequencing ◽  
Intestinal Flora ◽  
Albumin Level ◽  
Control Group ◽  
Sequencing Analysis ◽  
Dominant Type ◽  
Inflammatory Conditions ◽  
Rdna Sequencing ◽  
Family Level

Abstract Background Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy.Methods Patients were recruited during 2017-2019 and divided into healthy control group (CT), CKD non-dialysis group (CKD), hemodialysis group (HD) and peritoneal dialysis group (PD). Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed.Results Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae , Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport.Conclusion Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.

scholarly journals PAMK Relieves LPS-Induced Enteritis and Improves Intestinal Flora Disorder in Goslings

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Wanyan Li ◽  
Xuelian Xiang ◽  
Bingxin Li ◽  
Yifei Wang ◽  
Long Qian ◽  
...  
Keyword(s):  
Small Intestine ◽  
Morphological Changes ◽  
Intestinal Flora ◽  
The Body ◽  
Biologically Active ◽  
Rdna Sequencing ◽  
Positive Rate ◽  
Atractylodes Macrocephala ◽  
Serum Crp ◽  
The Impact

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a biologically active component of Atractylodes macrocephala, which has the effect of maintaining the immune homeostasis of the body. Therefore, this study constructed a model of PAMK to relieve LPS-induced gosling enteritis and observed the morphological changes of the small intestine after HE staining. ELISA was used to detect serum CRP, IL-1β, IL-6, and TNF-α levels; immunohistochemistry was used to detect the positive rate of IgA in the small intestine; TLR4, occludin, ZO-1, cytokines, and immunoglobulin mRNA expression in the small intestine were detected by qPCR; and intestinal flora of gosling excrement was analyzed by 16S rDNA sequencing to analyze the protective effect of PAMK on goslings enteritis and the impact on intestinal flora. The results showed that PAMK relieves LPS-induced gosling enteritis by maintaining the small intestine morphology, cytokine, tight junctions, and immunoglobulin relatively stable and improving the disorder of intestinal flora.

Protein convertase subtilisin/kexin type 9 biology in nephrotic syndrome: implications for use as therapy

2019 ◽  
Vol 35 (10) ◽  
pp. 1663-1674 ◽  
Author(s):  
Ruxandra Mihaela Busuioc ◽  
Adrian Covic ◽  
Mehmet Kanbay ◽  
Maciej Banach ◽  
Alexandru Burlacu ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Foam Cell ◽  
Regulatory Element ◽  
Cell Formation ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cumulative Effect ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Apoptosis Protein

Abstract Low-density lipoprotein cholesterol (LDL-C) levels almost constantly increased in patients with nephrotic syndrome (NS). Protein convertase subtilisin/kexin type 9 (PCSK9) [accelerates LDL-receptor (LDL-R) degradation] is overexpressed by liver cells in NS. Their levels, correlated inversely to LDL-R expression and directly to LDL-C, seem to play a central role in hypercholesterolaemia in NS. Hypersynthesis resulting from sterol regulatory element-binding protein dysfunction, hyperactivity induced by c-inhibitor of apoptosis protein expressed in response to stimulation by tumour necrosis factor-α produced by damaged podocytes and hypo-clearance are the main possible mechanisms. Increased LDL-C may damage all kidney cell populations (podocytes, mesangial and tubular cells) in a similar manner. Intracellular cholesterol accumulation produces oxidative stress, foam cell formation and apoptosis, all favoured by local inflammation. The cumulative effect of cellular lesions is worsened proteinuria and kidney function loss. Accordingly, NS patients should be considered high risk and treated by lowering LDL-C. However, there is still not enough evidence determining whether lipid-lowering agents are helpful in managing dyslipidaemia in NS. Based on good efficacy and safety proved in the general population, therapeutic modulation of PCSK9 via antibody therapy might be a reasonable solution. This article explores the established and forthcoming evidence implicating PCSK9 in LDL-C dysregulation in NS.

scholarly journals PSII-38 Tolerable upper intake levels of iron damage the intestine and alter the intestinal flora in weaned piglets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 381-381
Author(s):  
Haoxuan Ding ◽  
Jianan Han ◽  
Jie Feng
Keyword(s):  
Relative Abundance ◽  
Iron Supplementation ◽  
Intestinal Flora ◽  
Intestinal Barrier ◽  
Basal Diet ◽  
Duodenal Mucosa ◽  
Weaned Piglets ◽  
Iron Storage ◽  
Protein Levels ◽  
Weaned Piglet

Abstract Iron supplementation has been an intervention to improve iron storage and prevent iron deficiency anaemia in weaned piglets. NRC has set recommended nutrient intake (RNI) and tolerable upper intake levels (UL). The purpose of this study was to investigate the potential harm of UL iron to the gut and microbes of weaned piglets. Thirty 23-day old weaned piglets assigned to three dietary treatments: a basal diet supplemented with 100 (RNI), 300, or 3000 (UL) mg FeSO4/kg diet for 28 days. Piglets were then euthanized, and the gut and cecum microbes were collected. UL iron significantly reduced the height of the villi in the duodenum, ileum, and jejunum of weaned piglets, and showed duodenal mitochondrial swelling (P < 0.05). The addition of UL iron to the diet significantly reduced the expression of tight junction proteins Claudin-1, Occludin, and ZO-1 in weaned piglet duodenal mucosa (P < 0.05). The protein levels of DMT1 and Zip14 decreased (P < 0.05), and the protein levels of ferritin increased in the duodenal mucosa of UL iron fed weaned piglets (P < 0.05). Moreover, UL iron also increased the content of ROS and MDA and decreased the activity of SOD in the weaned piglet duodenal mucosa (P < 0.05). Additionally, UL iron significantly increased intestinal microbial diversity and species richness in weaned piglets. At the phylum level, UL iron supplementation was associated with a significant increase in Proteobacteria relative abundance, and significantly decreased the relative abundance of Firmicutes (P < 0.05). At the genus level, the relative abundance of Clostridiales, Faecalibacterium, and Prevotellaceae decreased significantly (P < 0.05), while the relative abundance of Desulfovibrio and Anaerovibrio increased significantly (P < 0.05). In conclusion, UL iron caused damage to the intestinal villi, damaged the intestinal barrier, reduced iron absorption, induced oxidative stress, led to histopathological changes, and modified the intestinal microbial structure in weaned piglets.

Sign in / Sign up

Export Citation Format

Share Document