A5013803657- Lipid metabolism and biosynthesis
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Enzyme Catalysis and Immobilization
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and disorders
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- Biofuel production and bioconversion
- Peroxisome Proliferator-Activated Receptors
- biodegradable polymer synthesis and properties
- RNA modifications and cancer
- Diabetes Treatment and Management
- Diet, Metabolism, and Disease
- Protein Degradation and Inhibitors
- Growth Hormone and Insulin-like Growth Factors
- Mitochondrial Function and Pathology
Umeå University
2023
Higher University of San Andrés
2023
Gilead Sciences (United States)
2020
University of California, San Francisco
2015-2018
Signature Research (United States)
2014
Duke-NUS Medical School
2012
Albert Einstein College of Medicine
2011
California Liver Research Institute
2007
The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae humans. Although much known regarding composition and catabolism lipid droplets, molecular components necessary for biogenesis have remained obscure. Here we report characterization a gene family important droplet formation named fat-inducing transcript (FIT). FIT1 FIT2 are endoplasmic reticulum resident membrane proteins that induce accumulation cell culture when expressed...
Abstract Background Animal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and drug discovery. Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a model fibrosing NASH. The present study directly assessed the clinical translatability by head-to-head comparison liver biopsy histological transcriptome changes GAN DIO-NASH mouse human patients. Methods C57Bl/6 J were fed chow or diet rich saturated fat (40%), fructose (22%) cholesterol...
Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although receptor homolog 1 (LRH-1) (encoded by NR5A2) suppressed in human NAFLD, evidence linking this phospholipid-bound nuclear to hepatic metabolism lacking. Here, we report essential role for LRH-1 storage and phospholipid composition based on acute KO adult mice (LRH-1AAV8-Cre mice). Indeed, LRH-1–deficient hepatocytes exhibited large cytosolic droplets increased triglycerides (TGs). fed...
SUMO-modification of nuclear proteins has profound effects on gene expression. However, non-toxic chemical tools that modulate sumoylation in cells are lacking. Here, to identify small molecule inhibitors we developed a cell-based screen focused the well-sumoylated substrate, human Liver Receptor Homolog-1 (hLRH-1, NR5A2). Our primary gene-expression assayed two SUMO-sensitive transcripts, APOC3 and MUC1, upregulated by SUMO-less hLRH-1 or siUBC9 knockdown, respectively. A polyphenol, tannic...
The global production of fossil-based plastics has reached critical levels, and their substitution with bio-based polymers is an urgent requirement. Poly(3-hydroxybutyrate) (PHB) a biopolymer that can be produced via microbial cultivation, but efficient microorganisms low-cost substrates are required. Halomonas boliviensis LC1, moderately halophilic bacterium, effective PHB producer, hydrolysates the residual stalks quinoa (Chenopodium Willd.) considered cheap source sugars for fermentation...
Triacylglyceride stored in cytosolic lipid droplets (LDs) constitutes a major energy reservoir most eukaryotes. The regulated turnover of triacylglyceride LDs provides fatty acids for mitochondrial β-oxidation and ATP generation physiological states high demand energy. mechanisms the formation conditions excess are not entirely understood. Fat storage-inducing transmembrane protein 2 (FIT2/FITM2) is anciently conserved member fat family proteins implicated to be important LDs, but its role...
Combination approaches for the treatment of NASH are being actively pursued. We examined effects administration a dual GLP-1 and glucagon receptor agonist (GLP-1:GCG, 0.015 mg/kg, s.c., q.d.) alone combined with an FXR (cilofexor, CILO; 30 mg/kg) and/or acetyl-CoA carboxylase inhibitor (firsocostat analog, ACCi; 5 both p.o., q.d) on endpoints in AMLN diet-induced biopsy-confirmed DIO-NASH mouse (n=15-16/group). After 12 weeks treatment, GLP-1:GCG reduced body weight 15%, slightly greater +...
Adipose tissue serves as the main storage depot of neutral lipids in cytosolic lipid droplets. We recently identified a two‐gene family proteins involved droplet biogenesis, which we name Fat storage‐Inducing Transmembrane protein (FITM1/FIT1 & FITM2/FIT2. FITM2 is ubiquitously expressed tissues with high expression white and brown adipose tissue. Overexpression either member FITM results increased accumulation droplets both vitro vivo, not by enhancing triglyceride synthesis but...
Cardiovascular disease and malignancy are the most common cause of death in Non-alcoholic Steatohepatitis (NASH) patients. Aside from lifestyle modification, there is currently no treatment for NASH. Activation Liver Receptor Homolog-1 (Lrh-1), known to bind phospholipid ligands, has been shown effectively reduce liver triglyceride (TG) DIO mice, raising Lrh-1 as a possible target treating Despite this finding, hepatic TGs equivalent controls liver-specific knockout (LKO or Lrh1 AlbCre )...
Semaglutide (SEMA), FXR agonists and ACC inhibitors are under active clinical investigation for the treatment of NASH. Here, we explored whether effects SEMA (0.12 mg/kg, s.c., q.d.) on NASH endpoints could be enhanced by addition an agonist (cilofexor, CILO; 30 mg/kg) and/or acetyl-CoA carboxylase inhibitor (firsocostat analogue, ACCi; 5 both p.o., in AMLN diet-induced biopsy-confirmed DIO-NASH mouse (n=15-16/group). After 12 weeks treatment, triple therapy reduced body weight 18%, being...