Faculty Opinions recommendation of Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression.

Inclusion of plant protein sources such as soyabean meal (SBM) in aquafeeds is associated with decreased lipid digestibility, reduced bile acid levels and hypocholesterolaemia. The mechanism for these metabolic abnormalities is unknown. The present study aimed at gaining further insight into how cholesterol and bile acid metabolism is modulated by SBM feeding by quantifying a number of mRNA species corresponding to key proteins involved in cholesterol and bile acid metabolism using quantitative real-time PCR. A 21 d feeding trial with sequential sampling at ten time points following initiation of 20 % SBM exposure was conducted on Atlantic salmon. A histological evaluation confirmed distal intestinal enteritis after 5 d of dietary exposure to the SBM, whereas diminished glycogen/lipid deposition was the only relevant finding observed in the liver. SBM inclusion resulted in reduced body pools of cholesterol and bile acids. Hepatic gene expression profiles revealed up-regulation of genes encoding rate-limiting enzymes in cholesterol (3-hydroxy-3-methyl-glutaryl-CoA reductase; HMGCR) and bile acid (cytochrome P4507A1 (CYP7A1)) biosynthesis, as well as up-regulation of their associated transcription factors (sterol regulatory element binding proteins 1 and 2, liver X receptor, farnesoid X receptor and PPAR isoforms). Hepatic gene expressions of cholesterol (ATP binding cassette G5 (ABCG5)) and bile acid (ATP binding cassette B11 (ABCB11)) transporters were, by and large, not influenced by the SBM, but distal intestinal expression patterns of ABCG5 and apical Na-dependent bile acid transporter indicated impaired cholesterol and bile acid reabsorption. In conclusion, hepatic gene expression profiles indicated that the capacity for cholesterol and bile acid synthesis was up-regulated, whereas the indicated impaired cholesterol and bile acid reabsorption probably occurred as a direct result of distal intestinal inflammation.

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Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms

Frontiers in Immunology ◽

10.3389/fimmu.2021.759276 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liu Liu ◽

Jiao Wang ◽

Hong-jin Li ◽

Shuo Zhang ◽

Meng-zhu Jin ◽

...

Keyword(s):

White Blood Cells ◽

Sphingosine Kinase ◽

Control Treatment ◽

Inflammatory Factors ◽

Spleen Weight ◽

Mrna Levels ◽

Receptor Agonists ◽

Sphingosine Kinase 2 ◽

Sphingosine 1 Phosphate ◽

S1p Receptor

BackgroundPsoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.ObjectiveTo assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.MethodsSix databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE’s risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.ResultsOne randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): −6.80; 95% confidence interval (CI): −8.23 to −5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: −0.95; 95% CI: −1.26 to −0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05).ConclusionsS1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.

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Abstract 296: Decreased Hepatic Avpr1a Gene Expression and Elevated Serum Bile Acid in Mouse Model of Metabolic Syndrome

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a296 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Xiaoya Ma ◽

Peter F Bodary

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Bile Acid ◽

Bile Acids ◽

Serum Bile Acid ◽

Hepatic Gene Expression ◽

Serum Bile Acids ◽

Kk Mice ◽

The Metabolic Syndrome

The KK/HIJ mouse has been demonstrated to have polygenic obesity and insulin resistance and serve as a model of metabolic syndrome. From microarray studies in this mouse strain, we observed hepatic gene expression of arginine vasopressin receptor 1A (Avpr1a) as the most differentially elevated gene in the liver following 3-week of voluntary wheel running activity. Subsequent studies validated that hepatic Avpr1a gene expression is significantly upregulated following voluntary activity and also highly suppressed (4 to 8-fold) in 2 independent models of insulin resistance (including obesity and lipoatrophic models). Although Avpr1a is highly abundant in the liver, its physiologic role is not well described. One proposed role for hepatic Avpr1a is mediation of vasopressin-induced bile acid secretion. To further evaluate the relationship between hepatic Avpr1a and bile acid homeostasis, we determined the age-related change in these variables in female KK mice. To investigate, adipose tissue, liver and serum were collected from female KK mice from before sexual maturity (PRE: 4.5 weeks old, n=9) and after sexual maturation (POST: 6 to 30 weeks old, n=12). Consistent with previous studies using this obesity-prone strain, we observed a robust increase in adiposity with age despite a standard rodent chow diet. RT-PCR studies of hepatic gene expression revealed a 53% lower Avpr1a in POST compared to PRE mice (p<0.00001). In parallel with the drop in hepatic Avpr1a gene expression was an increase in serum bile acids (PRE: 26.56± 9.98μmol/L; POST: 39.40± 9.63μmol/L; p<0.01). A negative correlation was evident between hepatic Avpr1a gene expression and serum bile acid level (R= -0.51). The change in Avpr1a and bile acids was pronounced at the age of onset of estrous cycling. In conclusion, female KK mice have a significant increase in fat mass with age in parallel with an elevation of serum bile acids and downregulation of hepatic Avpr1a gene expression. We propose that suppression of hepatic Avpr1a increases hydrophobic bile acids in the liver and serum and promotes hepatic inflammation, contributing to symptoms of the metabolic syndrome.

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Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salarL.)

British Journal Of Nutrition ◽

10.1017/s0007114513002717 ◽

2013 ◽

Vol 111 (3) ◽

pp. 432-444 ◽

Cited By ~ 52

Author(s):

Min Gu ◽

Trond M. Kortner ◽

Michael Penn ◽

Anne Kristine Hansen ◽

Åshild Krogdahl

Keyword(s):

Gene Expression ◽

Bile Acid ◽

Atlantic Salmon ◽

Lipid Droplet ◽

Expression Profiling ◽

Cholesterol Synthesis ◽

Plasma Cholesterol ◽

Lipid Absorption ◽

Hepatic Gene Expression ◽

Cholesterol Levels

Altered lipid metabolism has been shown in fish fed plant protein sources. The present study aimed to gain further insights into how intestinal and hepatic lipid absorption and metabolism are modulated by plant meal (PM) and soya-saponin (SA) inclusion in salmon feed. Post-smolt Atlantic salmon were fed for 10 weeks one of four diets based on fishmeal or PM, with or without 10 g/kg SA. PM inclusion resulted in decreased growth performance, excessive lipid droplet accumulation in the pyloric caeca and liver, and reduced plasma cholesterol levels. Intestinal and hepatic gene expression profiling revealed an up-regulation of the expression of genes involved in lipid absorption and lipoprotein (LP) synthesis (apo, fatty acid transporters, microsomal TAG transfer protein, acyl-CoA cholesterol acyltransferase, choline kinase and choline-phosphate cytidylyltransferase A), cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase) and associated transcription factors (sterol regulatory element-binding protein 2 and PPARγ). SA inclusion resulted in reduced body pools of cholesterol and bile salts. The hepatic gene expression of the rate-limiting enzyme in bile acid biosynthesis (cytochrome P450 7A1 (cyp7a1)) as well as the transcription factor liver X receptor and the bile acid transporterabcb11(ATP-binding cassette B11) was down-regulated by SA inclusion. A significant interaction was observed between PM inclusion and SA inclusion for plasma cholesterol levels. In conclusion, gene expression profiling suggested that the capacity for LP assembly and cholesterol synthesis was up-regulated by PM exposure, probably as a compensatory mechanism for excessive lipid droplet accumulation and reduced plasma cholesterol levels. SA inclusion had hypocholesterolaemic effects on Atlantic salmon, accompanied by decreased bile salt metabolism.

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Sphingosine kinase 2 plays a critical role in bile acid‐induced cholestatic liver injury via regulating miR‐155 and macrophage activation

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.07289 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Yuan Zhang ◽

Wilson Yang ◽

Yanyan Wang ◽

Runping Liu ◽

Xiaojiaoyang Li ◽

...

Keyword(s):

Bile Acid ◽

Liver Injury ◽

Macrophage Activation ◽

Critical Role ◽

Sphingosine Kinase ◽

Sphingosine Kinase 2 ◽

Cholestatic Liver Injury

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Effects of dietary broccoli fibre and corn oil on serum lipids, faecal bile acid excretion and hepatic gene expression in rats

Food Chemistry ◽

10.1016/j.foodchem.2011.09.117 ◽

2012 ◽

Vol 131 (4) ◽

pp. 1272-1278 ◽

Cited By ~ 16

Author(s):

Tafadzwa Mandimika ◽

Gunaranjan Paturi ◽

Cloe Erika De Guzman ◽

Christine A. Butts ◽

Katia Nones ◽

...

Keyword(s):

Gene Expression ◽

Bile Acid ◽

Serum Lipids ◽

Corn Oil ◽

Hepatic Gene Expression ◽

Acid Excretion ◽

Bile Acid Excretion

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The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000205 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0183-0195 ◽

Cited By ~ 12

Author(s):

Takashi Nakamura ◽

Tomoya Takeda ◽

Yoshihiko Tokuji

Keyword(s):

Gene Expression ◽

Immune Activation ◽

Expression Profiles ◽

Water Soluble ◽

Alpha Tocopherol ◽

Hepatic Gene Expression ◽

Tocopherol Concentration ◽

Altered Expression ◽

Atp Production ◽

Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

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