ABSTRACT
Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial-host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.
Subject(s)
Humans , Bile Acids and Salts/metabolism , Gastrointestinal Microbiome , Inflammation/metabolism , Metabolic Syndrome/metabolism , Receptors, Calcitriol/physiology , Receptors, Cytoplasmic and Nuclear/physiology , Receptors, G-Protein-Coupled/physiology , Signal Transduction/physiologyABSTRACT
O sistema endocrinológico vitamina D é constituído por um grupo de moléculas secosteroides derivadas do 7-deidrocolesterol, incluindo a forma ativa 1,25-diidroxi-vitamina D (1,25(OH)2D), seus precursores e metabólitos, sua proteína transportadora (DBP), seu receptor nuclear (VDR) e as enzimas do complexo do citocromo P450 envolvidas nos processos de ativação e inativação dessas moléculas. Os efeitos biológicos da 1,25(OH)2D são mediados pelo VDR, um fator de transcrição ativado por ligante, presente em quase todas as células humanas, e que pertence à família de receptores nucleares. Além dos clássicos papéis de reguladora do metabolismo do cálcio e da saúde óssea, as evidências sugerem que a 1,25(OH)2D module direta ou indiretamente cerca de 3 por cento do genoma humano, participando do controle de funções essenciais à manutenção da homeostase sistêmica, tais como crescimento, diferenciação e apoptose celular, regulação dos sistemas imunológico, cardiovascular e musculoesquelético, e no metabolismo da insulina. Pela influência crítica que esse sistema exerce em vários processos do equilíbrio metabólico sistêmico, é importante que os ensaios laboratoriais utilizados para sua avaliação apresentem alta acurácia e reprodutibilidade, permitindo que sejam estabelecidos pontos de corte que, além de serem consensualmente aceitos, expressem adequadamente o grau de reserva de vitamina D do organismo e reflitam os respectivos impactos clínico-metabólicos na saúde global do indivíduo.
The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)2D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)2D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)2D directly or indirectly modulates about 3 percent of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.
Subject(s)
Humans , Homeostasis/physiology , Signal Transduction/physiology , Steroid Hydroxylases/blood , Vitamin D Deficiency/diagnosis , Vitamin D/chemistry , Reference Values , Receptors, Calcitriol/physiologyABSTRACT
The vitamin D endocrine system, besides playing pivotal roles in calcium homeostasis & bone mineral metabolism, is now recognized to subserve a wide range of fundamental biological functions in cell differentiation, inhibition of cell growth as well as immuno modulation. Vitamin D is a prohormone which is converted into its active hormonal form 1, 25 (OH)D2 D, 1, 25 (OH)D2 D activates its cellular receptor (VDR) which activate target genes to engender its biological actions. This review provides a summary of recent understanding of the complex actions of the vitamin D hormone 1, 25 (OH)2 D which is a final product of 1alpha hydroxylation in the proximal tubular cells of kidneys. Emerging evidence also indicates both 1, 25 (OH)2 D3 independent as well as depended action of vitamin D receptor (VDR). Thus, the vitamin D system action may involve more than one single receptor and legand. The presence of 1alpha hydroxylase in many target cells other than proximal renal tubular cells indicates autocrine and paracrine functions for 1, 25 (OH)2 D3 in the control of cell proliferation and differentiation. Vitamin D and related molecules belong to a elaborate endocrine system that acts on target genomic receptors in several organ systems to control cell proliferation and differentiation.