A5046453964- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Alcohol Consumption and Health Effects
- Genetic Mapping and Diversity in Plants and Animals
- Retinoids in leukemia and cellular processes
- Innovations in Medical Education
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Lipid metabolism and biosynthesis
- Birth, Development, and Health
- Mitochondrial Function and Pathology
- Genetic and phenotypic traits in livestock
- Cytokine Signaling Pathways and Interactions
- Antioxidant Activity and Oxidative Stress
- Empathy and Medical Education
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- Obesity and Health Practices
- Immune Response and Inflammation
Case Western Reserve University
2013-2024
University School
2008-2024
Western University of Health Sciences
2008-2015
Xiaomi (China)
2011
Institut thématique Génétique, génomique et bioinformatique
1999-2011
Merck (Germany)
2005
MetroHealth
2003
Howard Hughes Medical Institute
2002
Princeton University
2002
National Institutes of Health
2001
The Mouse Metabolic Phenotyping Center (MMPC) Consortium was established to address the need characterize growing number of mouse models metabolic diseases, particularly diabetes and obesity. A goal MMPC is propose standard methods for assessing phenotypes in mice. In this article, we discuss issues pertaining design performance various tests glucose metabolism. We also guidelines description methods, presentation data interpretation results. recommendations presented article are based on...
Epidemiological studies indicate that the use of artificial sweeteners doubles risk for Crohn's disease (CD). Herein, we experimentally quantified impact 6-week supplementation with a commercial sweetener (Splenda; ingredients sucralose maltodextrin, 1:99, w/w) on both severity CD-like ileitis and intestinal microbiome alterations using SAMP1/YitFc (SAMP) mice.Metagenomic shotgun DNA sequencing was first used to characterize ileitis-prone SAMP mice. Then, 16S rRNA sequencing, quantitative...
Retinoic acid (RA) protects mice from diet-induced obesity. The activity is mediated in part through activation of the nuclear receptors RA (RARs) and peroxisome proliferator-activated receptor β/δ their associated binding proteins cellular protein type II (CRABP-II) fatty 5 adipocytes skeletal muscle, leading to enhanced lipid oxidation energy dissipation. It was also reported that inhibits differentiation cultured preadipocytes. However, whether hormone suppresses adipogenesis vivo how...
Hepatocellular carcinoma (HCC) is one of the leading causes cancer death worldwide, with ∼70% cases resulting from hepatitis B and C viral infections, aflatoxin exposure, chronic alcohol use or genetic liver diseases. The remaining ∼30% are associated obesity, type 2 diabetes related metabolic diseases, although a direct link between these pathologies HCCs has not been established. We tested long-term effects high-fat low-fat diets on males two inbred strains mice discovered that C57BL/6J...
The plasma membrane protein STRA6 is thought to mediate uptake of retinol from its blood carrier retinol-binding (RBP) into cells and function as a surface receptor that, upon binding holo-RBP, activates JAK/STAT cascade. It was suggested that signaling underlies insulin resistance induced by elevated serum levels RBP in obese animals. To investigate these activities vivo, we generated analyzed Stra6-null mice. We show the contribution tissues vivo small with exception eye, ablation Stra6...
Multiple pathways of programmed cell death are important in liver homeostasis. Hepatocyte is associated with progression nonalcoholic fatty disease, and inhibition apoptosis partially protects against injury response to a high‐fat diet (HFD). However, the contribution necroptosis, caspase‐independent pathway death, HFD‐induced not known. Wild‐type C57BL/6 receptor interacting protein (RIP) 3 −/− mice were randomized chow or HFD. HFD‐fed increased expression RIP3, master regulator as well...
Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that mediated via phosphorylation translation initiation factor eIF2α. It reported here chronic correlated increased islet and apoptosis vivo. Paradoxically, induced an anabolic transcription program overcome translational repression by eIF2α phosphorylation. This...
Issue: Calls to change medical education have been frequent, persistent, and generally limited alterations in content or structural re-organization. Self-imposed barriers prevented adoption of more radical pedagogical approaches, so recent predictions the 'inevitability' transitioning online delivery seemed unlikely. Then March 2020 COVID-19 pandemic forced schools overcome established overnight make most rapid curricular shift education's history. We share collated reports nine postulate...
Regulation of the turnover triglycerides in adipose tissue requires continuous provision 3-glycerophosphate, which may be supplied by metabolism glucose or glyceroneogenesis, de novo synthesis 3-glycerophosphate from sources other than hexoses glycerol. The importance glyceroneogenesis was assessed mice specifically eliminating expression cytosolic form phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role pathway. To accomplish this, we mutated binding site for...
The aim of this study was to investigate the role cytosolic form phosphoenolpyruvate carboxykinase (Pck1) in development insulin resistance. Previous studies have shown that roles Pck1 white adipose tissue (WAT) glyceroneogenesis and reesterification free fatty acids (FFA) generate triglyceride are vital for prevention diabetes. We hypothesized resistance develops when dysregulation occurs triglyceride/fatty acid cycle, which regulates lipid synthesis transport between liver. examined by...
Several components of the canonical pathway response to lipopolysaccharide (LPS) are required for EGF-dependent activation NFκB. Conversely, ability Toll-like Receptor 4 (TLR4) activate NFκB in LPS is impaired by down regulating EGF receptor (EGFR) expression or using EGFR inhibitor erlotinib. The LYN proto-oncogene (LYN) signaling both directions. binds upon stimulation, and erlotinib impairs this association. In mice, blocks LPS-induced tumor necrosis factor α (TNFα) interleukin-6 (IL-6)...
The gene for phosphoenolpyruvate carboxykinase (PEPCK), a target of CCAAT/enhancer-binding protein-α (C/EBPα) and -β (C/EBPβ), begins to be expressed in the liver at birth. Mice homozygous deletion CEBPα (C/EBPα−/− mice) die shortly after birth hypoglycemia, with no detectable hepatic PEPCK mRNA negligible glycogen stores. Half mice CEBPβ (C/EBPβ−/−mice) have normal glucose homeostasis (phenotype A), other half hypoglycemia due failure express mobilize B). Insulin deficiency induces C/EBPα...
The CCAAT/enhancer-binding protein beta (C/EBPbeta) is required for adipocyte differentiation and maturation. We have studied the role of transcription factor, C/EBPbeta, in development diet-induced obesity. Mice with a deletion gene C/EBPbeta (C/EBPbeta(-/-)) wild-type mice were fed high-fat diet (60% fat) 12 weeks. C/EBPbeta(-/-) lost body fat, whereas increased their total fat on diet. had lower levels blood triglycerides, free fatty acids, cholesterol, hepatic triglyceride accumulation...
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces the synthesis of 25-hydroxyvitamin 24-hydroxylase [24(OH)ase], an enzyme involved in its catabolism, thereby regulating own metabolism. Here we demonstrate that CCAAT enhancer binding protein beta (C/EBPbeta) is induced by 1,25(OH)(2)D(3) kidney and osteoblastic cells a potent vitamin D receptor (VDR)-mediated 24(OH)ase transcription. Transfection studies indicate induction transcription enhanced maximum 10-fold C/EBPbeta. Suppression...
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a stress response program that protects cells early and can lead to apoptosis during prolonged stress. basic leucine zipper transcription factor, CCAAT/enhancer-binding protein β (C/EBPβ), is one genes with increased expression ER Translation C/EBPβ mRNA from different initiation codons leads synthesis two transcriptional activators (LAP-1 −2) repressor (LIP). LIP/LAP ratio critical factor C/EBPβ-mediated gene...
Vitamin A is secreted from cellular stores and circulates in blood bound to retinol-binding protein (RBP). In turn, holo-RBP associates plasma with transthyretin (TTR) form a ternary RBP-retinol-TTR complex. It believed that binding TTR prevents the loss of RBP by filtration kidney. At target cells, recognized STRA6, membrane serves dual role: it mediates uptake retinol extracellular into functions as cytokine receptor that, upon holo-RBP, triggers JAK/STAT signaling cascade. We previously...
Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with expression of proinflammatory cytokines. Two these cytokines, interleukin-1 β (IL-1 ) IL-18, require activation caspase-1 via members the NOD-like receptor (NLR) family. These NLRs form an inflammasome that activated pathogens signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) CARD protein 4 (Nlrc4) have been studied...
Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat response cold-challenge maintain core body temperature essential for organismal survival. While cold activated mitochondrial biogenesis recognized as critical adaptation, the contribution quality control this process remains unclear. Here, we show mitophagy required brown adipocyte homeostasis during adaptation. Mitophagy significantly increased from cold-challenged mice...
Cancer cells in culture rely on glutamine as an anaplerotic substrate to replenish tricarboxylic acid (TCA) cycle intermediates that have been consumed. but it is uncertain whether cancers vivo depend for anaplerosis. Here, following infusions of [13C5]-glutamine mice bearing subcutaneous colon cancer xenografts, we showed substantial amounts infused enters the TCA tumors. Consistent with our prior observation colorectal (CRCs) oncogenic mutations phosphatidylinositol-4,5-bisphosphate...
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is enriched in liver and adipose tissue controls the expression of a wide variety genes coding for important metabolic pathways, including gluconeogenesis lipid synthesis. To investigate role C/EBPβ on glucose homeostasis, we studied mice with targeted deletion gene C/EBPβ–/– mice. Adult have hypoglycemia after an 18-hour fast, accompanied by lower hepatic production (40% that wild-type mice), no change plasma insulin...