showing 7 related works from this author
Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis.
2015
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. The relevance of VDR was assessed in apoE −/− mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR t…
An in-depth analysis shows a hidden atherogenic lipoprotein profile in non-diabetic chronic kidney disease patients
2019
Background: Chronic kidney disease (CKD) is an independent risk factor for atherosclerotic disease. We hypothesized that CKD promotes a proatherogenic lipid profile modifying lipoprotein composition and particle number. Methods: Cross-sectional study in 395 non-diabetic individuals (209 CKD patients and 186 controls) without statin therapy. Conventional lipid determinations were combined with advanced lipoprotein profiling by nuclear magnetic resonance, and their discrimination ability was assessed by machine learning. Results: CKD patients showed an increase of very-low-density (VLDL) particles and a reduction of LDL particle size. Cholesterol and triglyceride content of VLDLs and intermed…
Prevalence of Vertebral Fractures and Their Prognostic Significance in the Survival in Patients with Chronic Kidney Disease Stages 3‒5 Not on Dialysis
2020
Background: The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. Materials and Methods: 612 NDD 3‒5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral r…
Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism
2022
Vitamin D (VD) deficiency has been associated with cancer and diabetes. Insulin signaling through the insulin receptor (IR) stimulates cellular responses by activating the PI3K/AKT pathway. PTEN is a tumor suppressor and a negative regulator of the pathway. Its absence enhances insulin signaling leading to hypoglycemia, a dangerous complication found after insulin overdose. We analyzed the effect of VD signaling in a model of overactivation of the IR. We generated inducible double KO (DKO) mice for the VD receptor (VDR) and PTEN. DKO mice showed severe hypoglycemia, lower total cholesterol and increased mortality. No macroscopic tumors were detected. Analysis of the glucose metabolism did n…
Impaired Vitamin D Signaling in Endothelial Cell Leads to an Enhanced Leukocyte-Endothelium Interplay: Implications for Atherosclerosis Development
2015
Endothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while its deficiency is a risk factor for the progression of cardiovascular damage. Our aim was to assess the role of basal levels of vitamin D receptor (VDR) on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR) led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC) ro…
The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes.
2020
The vitamin D receptor (VDR) must be relevant to liver lipid metabolism because VDR deficient mice are protected from hepatosteatosis. Therefore, our objective was to define the role of VDR on the overall lipid metabolism in human hepatocytes. We developed an adenoviral vector for human VDR and performed transcriptomic and metabolomic analyses of cultured human hepatocytes upon VDR activation by vitamin D (VitD). Twenty percent of the VDR responsive genes were related to lipid metabolism, including MOGAT1, LPGAT1, AGPAT2, and DGAT1 (glycerolipid metabolism)
CKD NUTRITION, INFLAMMATION AND OXIDATIVE STRESS
2014
Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint w…