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Vdr lipid metabolism

Paolo Comeglio, Annamaria Morelli, Luciano Adorini, Mario Maggi, Linda Vignozzi
Bile acids act as steroid hormones, controlling lipid, glucose and energy metabolism, as well as inflammation and fibrosis. Their actions are implemented through activation of nuclear (FXR, VDR, PXR) and membrane G protein-coupled (TGR5, S1PR2) receptors. Areas covered: This review discusses the potential of FXR and TGR5 as therapeutic targets in the treatment of pulmonary disorders linked to metabolism and/or inflammation. Obeticholic acid (OCA) is the most clinically advanced bile acid-derived agonist for FXR-mediated anti-inflammatory and anti-fibrotic effects...
November 2017: Expert Opinion on Investigational Drugs
Imourana Alassane-Kpembi, Juliana Rubira Gerez, Anne-Marie Cossalter, Manon Neves, Joëlle Laffitte, Claire Naylies, Yannick Lippi, Martine Kolf-Clauw, Ana Paula L Bracarense, Philippe Pinton, Isabelle P Oswald
The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins...
August 8, 2017: Scientific Reports
Shiwei Li, Qi Li, Yuanyuan Kong, Shuang Wu, Qingpo Cui, Mingming Zhang, Shaobing O Zhang
Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
Francesca Silvagno, Gianpiero Pescarmona
Transcriptional control and modulation of calcium fluxes underpin the differentiating properties of vitamin D (1,25(OH)2D3). In the latest years however few studies have pointed out the relevance of the mitochondrial effects of the hormone. It is now time to focus on the metabolic results of vitamin D receptor (VDR) action in mitochondria, which can explain the pleiotropic effects of 1,25(OH)2D3 and may elucidate few contrasting aspects of its activity. The perturbation of lipid metabolism described in VDR knockout mice and vitamin D deficient animals can be revisited based on the newly identified mechanism of action of 1,25(OH)2D3 in mitochondria...
July 15, 2017: Molecular and Cellular Endocrinology
Renlong Li, Enshuang Guo, Jiankun Yang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
OBJECTIVE: 1,25(OH)2 D3 has been reported to attenuate liver steatosis; however, its exact mechanism of action remains poorly understood. This study aimed to determine whether 1,25(OH)2 D3 can attenuate hepatic steatosis by inducing autophagy. METHODS: Male C57BL/6 mice fed a high-fat diet (HFD) were injected with 1,25(OH)2 D3 for 4 weeks. These mice were given 3-methyladenine (3-MA) to inhibit autophagy. HepG2 cells were preincubated with a free fatty acid (FFA) and then treated with 1,25(OH)2 D3 ...
March 2017: Obesity
Nadja Engel, Anna Adamus, Nicolas Schauer, Juliane Kühn, Barbara Nebe, Guido Seitz, Karin Kraft
BACKGROUND: Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 μM) also promote proliferation of bone cancer cells in vitro. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective in vitro and in vivo. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts...
2017: PloS One
Alena Zolotarenko, Evgeny Chekalin, Alexandre Mesentsev, Ludmila Kiseleva, Elena Gribanova, Rohini Mehta, Ancha Baranova, Tatiana V Tatarinova, Eleonora S Piruzian, Sergey Bruskin
Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements...
November 4, 2016: Experimental & Molecular Medicine
Yosria E Aly, Azza S Abdou, Mona M Rashad, Menatallah M Nassef
This work aimed to study the effect of swimming exercise on serum vitamin D level and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus. Sixty adult male rats were divided into control and diabetic groups. Each was further subdivided into sedentary and exercised subgroups. Diabetes Mellitus was induced by a single intraperitoneal dose of streptozotocin (50 mg/kg) dissolved in cold 0.01 M citrate buffer (pH 4.5). The exercised subgroups underwent swimming for 60 min, 5 times a week for 4 weeks...
September 2016: Journal of Advanced Research
Raluca Haliga, F Zugun-Eloae, T Oboroceanu, A Pînzariu, Veronica Mocanu
Vitamin D (VitD), a lipid-soluble hormone, is able to regulate the transcription of many genes through vitamin D receptor (vitD receptor-VDR). It has been shown that VitD deficiency is associated with obesity, characterized by a low degree inflammatory state, which contribute to the pathogeny of metabolic syndrome and type 2 diabetes mellitus. VitD deficiency is a public health problem, at the same time the global prevalence of obesity and cardiovascular diseases is continuously growing. Evidence from recent studies on animal models suggest that VitD or VDR deficiency promotes cardiomyocyte hypertrophy, which can be one of the mechanisms for increasing cardiovascular risk...
April 2016: Revista Medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti Din Iaş̧i
Yue Fan, Kumi Futawaka, Rie Koyama, Yuki Fukuda, Misa Hayashi, Miyuki Imamoto, Takashi Miyawaki, Masato Kasahara, Tetsuya Tagami, Kenji Moriyama
BACKGROUND: The impact of vitamin D3 (VD3) on obesity has been reported in the past. Our study was aimed at investigating the possible mechanisms by which VD3 affects obesity induced by a high fat diet. METHODS: Eight-week-old C57BL/6 J male mice were fed a normal- or high-fat diet for 9 weeks and were treated with a gavage of vehicle (corn oil) or cholecalciferol (50 μg/kg, daily). Body weight, white adipose tissue weight, blood lipid and glucose levels were measured...
July 29, 2016: Journal of Biomedical Science
Milica Bozic, Carla Guzmán, Marta Benet, Sonia Sánchez-Campos, Carmelo García-Monzón, Eloi Gari, Sonia Gatius, José Manuel Valdivielso, Ramiro Jover
BACKGROUND & AIMS: The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. METHODS: The expression of liver VDR was investigated in apolipoprotein E knockout (apoE(-/-)) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis...
October 2016: Journal of Hepatology
Kent Wehmeier, Luisa M Onstead-Haas, Norman C W Wong, Arshag D Mooradian, Michael J Haas
The vitamin D metabolite 24,25-dihydroxyvitamin D3 (24, 25[OH]2D3) was shown to induce nongenomic signaling pathways in resting zone chondrocytes and other cells involved in bone remodeling. Recently, our laboratory demonstrated that 24,25-[OH]2D3 but not 25-hydroxyvitamin D3, suppresses apolipoprotein A-I (apo A-I) gene expression and high-density lipoprotein (HDL) secretion in hepatocytes. Since 24,25-[OH]2D3 has low affinity for the vitamin D receptor (VDR) and little is known with regard to how 24,25-[OH]2D3 modulates nongenomic signaling in hepatocytes, we investigated the capacity of 24,25-[OH]2D3 to activate various signaling pathways relevant to apo A-I synthesis in HepG2 cells...
August 2016: Journal of Molecular Endocrinology
Fei Yu, ChongJian Wang, Ling Wang, HongLin Jiang, Yue Ba, LingLing Cui, Yan Wang, SongCheng Yu, WenJie Li
BACKGROUND: Vitamin D and the vitamin D receptor (VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese. METHOD: Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function...
March 2017: Journal of Diabetes
Claudia D Fuchs, Stefan A Traussnigg, Michael Trauner
Nuclear receptors (NRs) are ligand-activated transcriptional regulators of several key metabolic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, and energy expenditure as well as inflammation, fibrosis, and cellular proliferation in the liver. Dysregulation of these processes contributes to the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD). This places NRs at the forefront of novel therapeutic approaches for NAFLD. Some NRs are already pharmacologically targeted in metabolic disorders such as hyperlipidemia (peroxisomal proliferator-activated receptor α [PPARα], fibrates) and diabetes (PPARγ, glitazones) with potential applications for NAFLD...
February 2016: Seminars in Liver Disease
O A Makeeva, A A Sleptsov, E V Kulish, O L Barbarash, A M Mazur, E B Prokhorchuk, N N Chekanov, V A Stepanov, V P Puzyrev
Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non-random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted...
July 2015: Acta Naturae
Ana Vuica, Lejla Ferhatović Hamzić, Katarina Vukojević, Milka Jerić, Livia Puljak, Ivica Grković, Natalija Filipović
Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats...
December 2015: Experimental Gerontology
Julia Marianne Hoffmann, Linda Partridge
Health during aging can be improved by genetic, dietary and pharmacological interventions. Many of these increase resistance to various stressors, including xenobiotics. Up-regulation of xenobiotic detoxification genes is a transcriptomic signature shared by long-lived nematodes, flies and mice, suggesting that protection of cells from toxicity of xenobiotics may contribute to longevity. Expression of genes involved in xenobiotic detoxification is controlled by evolutionarily conserved transcriptional regulators...
2015: Critical Reviews in Biochemistry and Molecular Biology
Aaron L Slusher, Matthew J McAllister, Chun-Jung Huang
Vitamin D plays an essential role in the regulation of skeletal metabolism as well as calcium and phosphate homeostasis, while vitamin D receptor (VDR) regulates de novo lipid synthesis, thereby contributing to the development of obesity. Furthermore, obese individuals are at a greater risk for vitamin D deficiency which may increase the potential risk for chronic inflammation, insulin resistance, and metabolic syndrome. While acute exercise enhances the activation of inflammatory signaling pathways, chronic exercise training may attenuate elevated pro-inflammatory cytokine production, resulting in the improvement of cardiovascular and metabolic health in obese individuals...
August 2015: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Yan Ding, Wang Liao, Zhuwen Yi, Wei Xiang, Xiaojie He
Atherosclerosis is the key course of coronary heart disease. In this study, we investigated the effect of vitamin D receptor on serum 1,25-(OH)2D levels, lipid profiles, nitric oxide expression, apoptosis-related gene Bcl-2, fas protein levels, in ApoE-deficient mice. The proliferation activity of VDR-RNAi transfected endothelial cells was decreased, the ability of apoptosis was increased, nitric oxide concentration was decreased and eNOS protein level was significantly reduced. VDR-RNAi induced lipid metabolism abnormality, reduced eNOS and ApoE levels, promoted lipid peroxidation, damaged the endothelial function and accelerated the process of atheroscleros...
2015: International Journal of Clinical and Experimental Medicine
Ester Gonzalez-Sanchez, Delphine Firrincieli, Chantal Housset, Nicolas Chignard
BACKGROUND: Nuclear receptors (NRs) form a family of 48 members. NRs control hepatic processes such as bile acid homeostasis, lipid metabolism and mechanisms involved in fibrosis and inflammation. Due to their central role in the regulation of hepatoprotective mechanisms, NRs are promising therapeutic targets in cholestatic disorders. KEY MESSAGES: NRs can be classified into five different physiological clusters. NRs from the 'bile acids and xenobiotic metabolism' and from the 'lipid metabolism and energy homeostasis' clusters are strongly expressed in the liver...
2015: Digestive Diseases
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