A5079262202- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Hormonal and reproductive studies
- Estrogen and related hormone effects
- Peroxisome Proliferator-Activated Receptors
- Liver Diseases and Immunity
- Fatty Acid Research and Health
- Diet and metabolism studies
- Cholesterol and Lipid Metabolism
- Prostate Cancer Treatment and Research
- Adipose Tissue and Metabolism
- Pediatric Hepatobiliary Diseases and Treatments
- Cancer therapeutics and mechanisms
- Metabolism, Diabetes, and Cancer
- Metabolomics and Mass Spectrometry Studies
- Diet, Metabolism, and Disease
- Eicosanoids and Hypertension Pharmacology
- Neonatal Health and Biochemistry
- Gallbladder and Bile Duct Disorders
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Hypoxia, and Metabolism
- Alcohol Consumption and Health Effects
- Metabolism and Genetic Disorders
Université Laval
2016-2025
Centre hospitalier universitaire de Québec
2010-2024
University of California, San Diego
2015-2021
Hôpital d'Instruction des Armées Sainte-Anne
2021
Quebec Research and Development Centre
2015-2021
Shiga University of Medical Science
2021
Showa University
2020
University of Lisbon
2015
Universidade do Porto
2015
University of British Columbia
2013
Objective The consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu ( Myrciaria dubia ) an Amazonian fruit a unique phytochemical profile, strong antioxidant potential purported anti-inflammatory potential. Design By using metabolic tests coupled 16S rRNA gene-based taxonomic profiling faecal microbial transplantation (FMT), we have assessed effect crude extract (CC) on obesity immunometabolic disorders high...
An increased prevalence of hypertriglyceridemia and gallbladder disease occurs in patients with diabetes or insulin resistance. Hypertriglyceridemia is positively associated to gall bladder risk. The farnesoid X receptor (FXR) a bile acid-activated nuclear that plays key role acid triglyceride homeostasis. mechanisms controlling FXR gene expression are poorly understood. This study evaluated whether regulated by alterations glucose was decreased livers streptozotocin-induced diabetic rats...
Statins are inhibitors of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase used in the prevention cardiovascular disease (CVD). In addition to their cholesterol-lowering activities, statins exert pleiotropic antiinflammatory effects, which might contribute beneficial effects not only on CVD but also lipid-unrelated immune and inflammatory diseases, such as rheumatoid arthritis, asthma, stroke, transplant rejection. However, molecular mechanisms involved these properties unresolved....
Bile acids (BAs) play critical physiological functions in cholesterol homeostasis, and deregulation of BA metabolism causes cholestatic liver injury. The long noncoding RNA maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor; however, its basic hepatic function remains elusive. Using pull-down with biotin-labeled sense or anti-sense MEG 3RNA followed by mass spectrometry, we identified RNA-binding protein polypyrimidine tract-binding 1 (PTBP1) MEG3...
Based on our recent finding that disruption of bile acid (BA) homeostasis in mice results the induction hepatic long noncoding RNA H19 expression, we sought to elucidate role cholestatic liver fibrosis. Hepatic overexpression H19RNA augmented duct ligation (BDL)-induced fibrosis, which was accompanied by elevation serum alanine aminotransferase, aspartate bilirubin, and BA levels. Multiple genes related inflammation, biliary hyperplasia were increased H19-BDL versus null-BDL mice, whereas...
Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation UDCA withdrawal in group consecutive PSC. Twenty six patients, all treated (dose range: 10-15 mg/kg/day) were included. Paired blood samples liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) collected before 3 months later. Liquid chromatography/tandem mass spectrometry was used quantification 29 plasma...
Significance Camptothecin (CPT)-11 (irinotecan) is an antitumor agent used in cancer chemotherapy primarily for the treatment of solid tumors. CPT-11 a prodrug that metabolized by carboxylesterases to DNA topoisomerase 1 inhibitor, called SN-38. Detoxification SN-38 occurs UDP-glucuronosyltransferase 1A1 (UGT1A1)-dependent glucuronidation. A serious side effect SN-38–induced intestinal toxicity, which believed result part from delivery into tissue through enterohepatic circulation. By...
Abstract Bile acid (BA) metabolism is tightly controlled by nuclear receptor signaling to coordinate regulation of BA synthetic enzymes and transporters. Here we reveal a molecular cascade consisting the antiapoptotic protein BCL2, Shp long non-coding RNA (lncRNA) H19 maintain homeostasis. Bcl2 was overexpressed in liver C57BL/6J mice using adenovirus mediated gene delivery for two weeks. Hepatic overexpression caused drastic accumulation serum bilirubin levels dysregulated reactivation...
Uncontrolled inflammation participates in the development of inflammatory diseases. Beneficial effects polyunsaturated fatty acids belonging to n-3 family such as eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) on have been reported. The present study investigates basal EPA, DHA a mixture EPA + expression 10 genes (AKT1, MAPK, NFKB, TNFA, IL1Β, MCP1, ALOX5, PTGS2, MGST1 NOS2) related unstimulated cultured THP1 macrophages. Cells were incubated for 24 h with PUFAs (50 μM DHA, DHA)....
Abstract Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show dietary intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance liver steatosis a mouse model obesity-linked diabetes. Fecal microbiota transplantation studies reveal effects are partly linked to gut microbiota. We further impacts metabolome, notably maintaining levels branched chain...
3'-Azido-3'-deoxythymidine (AZT) is frequently prescribed to patients infected with the human immunodeficiency virus. After absorption, AZT rapidly metabolized into 3'-azido-3'-deoxy-5'-glucuronylthymidine by UDP-glucuronosyltransferase (UGT) enzymes. Using labeled [(14)C]UDP-glucuronic acid and microsomal preparations from kidney 293 cells stably expressing different UGT2B isoenzymes, it was demonstrated that glucuronidation catalyzed specifically UGT2B7. The identity of metabolite formed...
Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARα nuclear receptor controlling lipid metabolism and inflammation, but its role the regulation of growth remains to be established. Here, we show that controls cell-cycle progression at G1/S transition by targeting cyclin-dependent kinase inhibitor tumor suppressor p16INK4a (p16), resulting an inhibition retinoblastoma protein phosphorylation. activates p16 gene transcription both binding canonical...
Peroxisome proliferator activated-receptor alpha (PPARalpha) is a ligand-activated transcription factor belonging to the nuclear receptor family. PPARalpha implicated in regulation of lipid and glucose metabolism control inflammatory response. Recently, it has been demonstrated that number receptors are degraded by ubiquitin-proteasome pathway. Since exhibits circadian expression rhythm since rapidly regulated under certain pathophysiological conditions such as acute phase response, we...
Glucuronidation, a major metabolic pathway for large variety of endobiotics and xenobiotics, is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) family. Among UGT enzymes, UGT2B4 conjugates endogenous exogenous molecules considered be bile acid conjugating enzyme in human liver. In present study, we identify as novel target gene nuclear receptor peroxisome proliferator-activated α (PPARα), which mediates hypolipidemic action fibrates. Incubation hepatocytes or...
The human UDP-glucuronosyltransferase 1 (UGT1) locus spans nearly 200 kb on chromosome 2 and encodes nine UGT1A proteins that play a prominent role in drug xenobiotic metabolism. Transgenic UGT1 (Tg-UGT1) mice have been created, it has demonstrated tissue-specific receptor control of the genes is influenced through circulating humoral factors. In Tg-UGT1 mice, are differentially expressed liver gastrointestinal tract. Gene expression profiles confirmed all can be targeted for regulation by...
Chenodeoxycholic acid (CDCA) is a liver-formed detergent and plays an important role in the control of cholesterol homeostasis. During cholestasis, toxic bile acids (BA) accumulate hepatocytes causing damage consequent impairment their function. Glucuronidation, conjugation reaction catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, considered metabolic pathway for hepatic BA. This study identifies human UGT1A3 enzyme as major responsible formation acyl CDCA-24glucuronide (CDCA-24G)....
The <i>UDP-glucuronosyltransferase</i> (<i>UGT</i>) <i>1A</i> genes in humans have been shown to be differentially regulated a tissue-specific fashion. Transgenic mice carrying the human <i>UGT1</i> locus (Tg-<i>UGT1</i>) were recently created, demonstrating that expression of nine <i>UGT1A</i> closely resembles patterns observed tissues. In present study, UGT1A1, UGT1A3, UGT1A4, and UGT1A6 identified as targets peroxisome proliferator-activated receptor (PPAR) α hepatocytes Tg-<i>UGT1</i>...
Uridine diphosphate-glucuronosyltransferase 2 (UGT2)B15 and B17 enzymes conjugate dihydrotestosterone (DHT) its metabolites androstane-3alpha, 17beta-diol (3alpha-DIOL) androsterone (ADT). The presence of UGT2B15/B17 in the epithelial cells human prostate has been clearly demonstrated, significant 3alpha-DIOL glucuronide ADT-glucuronide concentrations have detected this tissue. androgen-dependent cancer cell line, LNCaP, expresses UGT2B15 -B17 is also capable conjugating androgens. To assess...
Bile acids are considered as extremely toxic at the high concentrations reached during bile duct obstruction, but each acid displays variable cytotoxic properties. This study investigates how biliary obstruction and restoration of flow interferes with urinary circulating levels 17 common acids. (conjugated unconjugated) were quantified by liquid chromatography coupled tandem mass spectrometry in serum urine samples from patients (8 men 9 women) before after stenting. Results compared...