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Vdr ppar

Borja Bandera Merchan, Francisco José Tinahones, Manuel Macías-González
The PPAR nuclear receptor family has acquired great relevance in the last decade, which is formed by three different isoforms (PPARα, PPARβ/δ, and PPAR ϒ). Those nuclear receptors are members of the steroid receptor superfamily which take part in essential metabolic and life-sustaining actions. Specifically, PPARG has been implicated in the regulation of processes concerning metabolism, inflammation, atherosclerosis, cell differentiation, and proliferation. Thus, a considerable amount of literature has emerged in the last ten years linking PPARG signalling with metabolic conditions such as obesity and diabetes, cardiovascular disease, and, more recently, cancer...
2016: PPAR Research
Marta Domínguez, Susana Alvarez, Angel R de Lera
Retinoid X receptors (RXRs) are promiscuous partners of heterodimeric associations with other members of the Nuclear Receptor (NR) superfamily. Through these liaisons RXR ligands ("rexinoids") either transcriptionally activate on their own the "permissive" subclass of heterodimers (PPAR/RXR, LXR/RXR, FXR/RXR) or synergize with partner ligands in the "non-permissive" subclass of heterodimers (RAR/RXR, VDR/RXR and TR/RXR). The nature and extent of the interaction of the ligand-receptor complexes with co-regulators, which is cell and context-dependent, results ultimately in transcriptional modulation of cognate gene networks...
June 16, 2016: Current Topics in Medicinal Chemistry
Carl E Wagner, Peter W Jurutka, Pamela A Marshall, Michael C Heck
Since the isolation and identification of the retinoid X receptor (RXR) as a member of the nuclear receptor (NR) superfamily in 1990, its analysis has ushered in a new understanding of physiological regulation by nuclear receptors, and novel methods to identify other unknown and orphan receptors. Expression of one or more of the three isoforms of RXR-α, β, and ϒ- can be found in every human cell type. Biologically, RXR plays a critical role through its ability to partner with other nuclear receptors. RXR is able to regulate nutrient metabolism by forming "permissive" heterodimers with peroxisome proliferator-activated receptor (PPAR), liver-X-receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which function when ligands are bound to one or both of the heterodimer partners...
June 16, 2016: Current Topics in Medicinal Chemistry
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
Lena Ekström, Ilona Skilving, Marie-Louise Ovesjö, Eleni Aklillu, Hanna Nylén, Anders Rane, Ulf Diczfalusy, Linda Björkhem-Bergman
Previous in vitro studies have shown that microRNA-27b (miR-27b) may regulate mRNA levels of CYP3A4, vitamin D receptor (VDR), and Peroxisome proliferator-activated receptor α (PPAR α) as well as CYP3A4 protein expression and activity. In vitro studies have also shown that vitamin D may affect the expression of CYP3A4. The primary aim of this pilot study was to investigate the association between miR-27b and CYP3A expression and activity. The secondary aim was to investigate the association between 25-hydroxy vitamin D in serum and CYP3A activity...
December 2015: Pharmacology Research & Perspectives
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
Jessica Lopes Nobre, Patricia C Lisboa, Nayara Peixoto-Silva, Fernanda Torres Quitete, Janaine C Carvalho, Egberto Gaspar de Moura, Elaine de Oliveira
SCOPE: Early weaning (EW) is associated with an impairment of offspring development and leads to overweight and higher 25-hydroxyvitamin D (25(OH)D) levels in adulthood, which can be corrected by calcium supplementation, potentially via vitamin D regulation of adipogenesis. METHODS AND RESULTS: We examined vitamin D status in adipose tissue in EW obese rats, treated with calcium. Dams were separated into: EW- dams were wrapped with a bandage to interrupt lactation (last 3 days), and C- pups with free access to milk...
April 2016: Molecular Nutrition & Food Research
Mehrnoosh Khodaeian, Samaneh Enayati, Ozra Tabatabaei-Malazy, Mahsa M Amoli
INTRODUCTION: Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is influenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iranian populations. METHODS: Google Scholar, PubMed, Scopus, and Persian web databases were systematically searched up to January 2014. The search terms were "gene," "polymorphism," "diabetes," and "diabetic complications"; nephropathy, retinopathy, neuropathy, foot ulcer, and CAD (coronary artery diseases); and Persian equivalents...
2015: Journal of Diabetes Research
Kenji Moriyama, Hiroyuki Yamamoto, Kumi Futawaka, Asami Atake, Masato Kasahara, Tetsuya Tagami
Thyroid hormone exerts a pleiotropic effect on development, differentiation, and metabolism through thyroid hormone receptor (TR). A novel thyroid hormone receptor β isoform (TRβ4) was cloned using PCR from a human pituitary cDNA library as a template. We report here the characterization of TRβ4 from a molecular basis. Temporal expression of TRβ4 during the fetal period is abundant in the brain and kidney, comparable with the adult pattern. Western blot analysis revealed that TRs are ubiquitination labile proteins, while TRβ1 is potentially stable...
2016: Endocrine Research
Kirtimaan Syal, Anand Srinivasan, Dibyajyoti Banerjee
Diabetes and tuberculosis are world's most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-γ (PPARγ) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis...
July 2015: Indian Journal of Clinical Biochemistry: IJCB
Robert C Baxter
In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ)...
September 10, 2015: Gene
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
Eva Morales, Manuel Sanchez-Solis, Luis Garcia-Marcos
Asthma and allergy are complex diseases influenced by poorly understood environmental and genetic factors. The innate and adaptive immune systems play an important role in the pathogenesis of these diseases. Many genes involved in inflammation and immunoregulation pathways have been related to asthma and allergy susceptibility. Among the diverse extra-skeletal actions of vitamin D, growing evidence indicates that vitamin D is an important modulator of the immune system response and may influence the development of asthma and allergy susceptibility through different mechanisms...
2015: Mini Reviews in Medicinal Chemistry
Xiaoliang Zhang, Min Zhou, Yinfeng Guo, Zhixia Song, Bicheng Liu
Macrophages, especially their activation state, are closely related to the progression of diabetic nephropathy. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. 1,25-Dihydroxyvitamin D3 has renoprotective roles that extend beyond the regulation of mineral metabolism, and PPARγ, a nuclear receptor, is essential for macrophage polarization. The present study investigates the effect of 1,25-dihydroxyvitamin D3 on macrophage activation state and its underlying mechanism in RAW264...
2015: BioMed Research International
Jisu Oh, Amy E Riek, Isra Darwech, Katsuhiko Funai, JianSu Shao, Kathleen Chin, Oscar L Sierra, Geert Carmeliet, Richard E Ostlund, Carlos Bernal-Mizrachi
Intense effort has been devoted to understanding predisposition to chronic systemic inflammation because it contributes to cardiometabolic disease. We demonstrate that deletion of the macrophage vitamin D receptor (VDR) in mice (KODMAC) is sufficient to induce insulin resistance by promoting M2 macrophage accumulation in the liver as well as increasing cytokine secretion and hepatic glucose production. Moreover, VDR deletion increases atherosclerosis by enabling lipid-laden M2 monocytes to adhere, migrate, and carry cholesterol into the atherosclerotic plaque and by increasing macrophage cholesterol uptake and esterification...
March 24, 2015: Cell Reports
Stina Betts, Linda Björkhem-Bergman, Anders Rane, Lena Ekström
Previous reports have suggested that the nuclear receptors vitamin D receptor (VDR), peroxisome proliferator-activated receptor α (PPARα), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are involved in the regulation of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 expression in adults. The aim of this study was to investigate the gene expression of CYP3A4 and the foetal CYP3A7 in human foetal tissues and their relation to gene expression and genetic variations in the nuclear receptors VDR, PPARα, PXR and CAR...
October 2015: Basic & Clinical Pharmacology & Toxicology
Kelly Teske, Premchendar Nandhikonda, Jonathan W Bogart, Belaynesh Feleke, Preetpal Sidhu, Nina Yuan, Joshua Preston, Robin Goy, Leggy A Arnold
Herein we describe the evaluation of GW0742 analogs in respect to their ability to modulate transcription mediated by the vitamin D receptor (VDR) and the peroxisome proliferator activated receptor (PPAR) δ. The GW0742 analog bearing a carboxylic ester functionality in place of the carboxylic acid was partially activating both nuclear receptors at low concentration and inhibited transcription at higher compound concentrations. The GW0742 alcohol derivative was more active than the ester in respect to VDR but less active in regard to PPARδ...
2014: Journal of Biomolecular Research & Therapeutics
Carolyn J Ricciardi, Jiyoung Bae, Debora Esposito, Slavko Komarnytsky, Pan Hu, Jiangang Chen, Ling Zhao
PURPOSE: The vitamin D system plays a role in metabolism regulation. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) suppressed 3T3-L1 white adipocyte differentiation. Vitamin D receptor (VDR) knockout mice showed increased energy expenditure, whereas mice with adipose-specific VDR over-expression showed decreased energy expenditure. Brown adipose tissue (BAT), now known to be present in adult humans, functions in non-shivering thermogenesis by uncoupling ATP synthesis from respiration and plays an important role in energy expenditure...
September 2015: European Journal of Nutrition
Hugh Salamon, Natalie Bruiners, Karim Lakehal, Lanbo Shi, Janani Ravi, Ken D Yamaguchi, Richard Pine, Maria Laura Gennaro
Vitamin D has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat because of multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. In this article, we report a novel, metabolic role for vitamin D in tuberculosis identified through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed an association between vitamin D receptor (VDR) and lipid metabolism in human tuberculosis and infected macrophages...
July 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
K Mirzaei, A Hossein-Nezhad, S A Keshavarz, S M Eshaghi, F Koohdani, A A Saboor-Yaraghi, S Hosseini, A Tootee, M Djalali
AIM: Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance...
February 2014: Minerva Medica
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