A5028307612- Liver Disease Diagnosis and Treatment
- Peroxisome Proliferator-Activated Receptors
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Drug Transport and Resistance Mechanisms
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Lipid metabolism and disorders
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Cholesterol and Lipid Metabolism
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Liver physiology and pathology
- Developmental Biology and Gene Regulation
- Bone Metabolism and Diseases
- Cancer-related gene regulation
- Connective tissue disorders research
- TGF-β signaling in diseases
- ATP Synthase and ATPases Research
- Fibroblast Growth Factor Research
- Alcohol Consumption and Health Effects
- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Helicobacter pylori-related gastroenterology studies
Drexel University
2023-2025
Washington University in St. Louis
2015-2024
Vehicle Technologies Office
2009
University of Missouri–St. Louis
2003-2009
Immunovaccine (Canada)
2007
The disaccharide trehalose blocks glucose uptake in hepatocytes and induces autophagy that prevents fatty liver disease.
Liver fatty acid-binding protein (L-Fabp) is an abundant cytosolic lipid-binding with broad substrate specificity, expressed in mammalian enterocytes and hepatocytes. We have generated mice a targeted deletion of the endogenous L-Fabp gene characterized their response to alterations hepatic acid flux following prolonged fasting. Chow-fed L-Fabp<sup>–/–</sup> were indistinguishable from wild-type littermates regard growth, serum tissue lipid profiles, distribution within complex species. In...
Liver fatty acid-binding protein (L-Fabp) regulates murine hepatic acid trafficking in response to fasting. In this study, we show that L-Fabp(-/-) mice fed a high-fat Western diet for up 18 weeks are less obese and accumulate triglyceride than C57BL/6J controls. Paradoxically, both control manifested comparable glucose intolerance insulin resistance when diet. Protection against obesity diet-fed was not due discernable changes food intake, fat malabsorption, or heat production, although...
Background and Aims Human transmembrane 6 superfamily 2 ( TM6SF2 ) variant rs58542926 is associated with NAFLD HCC. However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased very low density lipoprotein (VLDL) secretion either unchanged increased hepatic steatosis, fibrosis. We generated liver‐specific Tm6Sf2 (Tm6 LKO) to study VLDL the impact on development progression of NAFLD. Approach Results Two independent lines Tm6 LKO exhibited spontaneous...
We previously identified subsets of patients with NAFLD different metabolic phenotypes. Here we align metabolomic signatures cardiovascular disease (CVD) and genetic risk factors.
Osteocalcin (OC) is a small calcium binding protein expressed in bones and teeth undergoing mineralization. OC expression calvarial osteoblasts odontoblasts regulated part via protein−protein interactions between the homeodomain repressor, Msx2, components of cell type-specific basal promoter. Recent work suggests that proteins form heterodimers confer transcriptional regulation. Since Dlx5 Msx2 are both by primary rat osteoblasts, we examined whether functionally interact to regulate In...
Microsomal TG transfer protein (MTTP) is required for the assembly and secretion of (TG)-rich lipoproteins from both enterocytes hepatocytes. Liver-specific deletion Mttp produced a dramatic reduction in plasma very low density lipoprotein-TG virtually eliminated apolipoprotein B100 (apoB100) yet caused only modest reductions apoB48 primary These observations prompted us to examine phenotype following intestine-specific because murine, like human enterocytes, secrete exclusively apoB48. We...
Liver regeneration is impaired following partial hepatectomy (PH) in mice with genetic obesity and hepatic steatosis also wild-type fed a high-fat diet. These findings contrast other data showing that liver which lipid accumulation suppressed by either pharmacologic leptin administration or disrupted glucocorticoid signaling. latter suggest may actually be required for normal regeneration. We have reexamined this relationship using several murine models of altered metabolism. fatty acid (FA)...
Activation of hepatic stellate cells (HSCs) is crucial to the development fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that acid-binding protein (L-Fabp), an abundant cytosolic modulates acid (FA) metabolism enterocytes and hepatocytes, also HSC FA utilization turn regulates L-Fabp expression decreased 10-fold following activation, concomitant with LDs. Primary...
Interstitial collagenases participate in the remodeling of skeletal matrix and are regulated by fibroblast growth factor (FGF). A 0.2-kb fragment proximal human interstitial collagenase [matrix metalloproteinase (MMP1)] promoter conveys 4- to 8-fold induction a luciferase reporter response FGF2 MC3T3-E1 osteoblasts. By 5′-deletion, this maps nucleotides− 100 −50 relative transcription initiation site. The 63- bp MMP1 −123 −61 confers on rous sarcoma virus minimal promoter. Intact Ets AP1...
FA transport protein 4 (FATP4), one member of a multigene family transporters, was proposed as major transporter in intestinal lipid absorption. Due to the fact that Fatp4(-/-) mice die because perinatal skin defect, we rescued phenotype using an FATP4 transgene driven by keratinocyte-specific promoter (Fatp4(-/-);Ivl-Fatp4(tg/+) mice) elucidate role dietary Fatp4(-/-);Ivl-Fatp4(tg/+) and wild-type littermates displayed indistinguishable food consumption, growth, weight gain on either low or...
Protein cysteine is susceptible to diverse oxidations, including disulfide, S-sulfenylation, S-nitrosylation, and S-glutathionylation, that regulate many biological processes in physiology diseases. Despite evidence supporting distinct outcomes of individual oxoforms, the approach for examining functional effects resulting from a specific oxoform, such as remains limited. In this report, we devised dehydroglutathione (dhG)-mediated strategy, named G-PROV, introduces non-reducible...
Msx2 is a homeodomain transcriptional repressor that exerts tissue-specific actions during craniofacial skeletal and neural development. To identify coregulatory molecules participate in repression by Msx2, we applied Farwestern expression cloning strategy to transcripts encoding proteins bind Msx2. A λgt11 library from mouse brain was screened with radiolabeled GST-Msx2 fusion protein encompassing the core suppressor domain of cDNA isolated encodes novel fragment binds Homeoprotein binding...
Liver fatty acid (FA)-binding protein (L-Fabp), a cytoplasmic expressed in liver and small intestine, regulates FA trafficking vitro plays an important role diet-induced obesity. We observed that L-Fabp −/− mice are protected against Western obesity hepatic steatosis. These findings conflict, however, with another report of exaggerated increased steatosis female fed cholesterol-supplemented diet. To resolve this apparent paradox, we two different low-fat diets discovered (on both diets)...
Unlike the livers of humans and mice, most hepatoma cells, which accumulate triglycerides when treated with microsomal triglyceride transfer protein (MTP) inhibitors, L35 rat cells do not express MTP cannot secrete very low density lipoprotein (VLDL), yet they triglyceride. In these studies we show that transcriptional co-repression two lipid proteins, liver fatty acid-binding (L-FABP) MTP, cooperatively shunt acids into de novo synthesized glycerolipids lipids VLDL, respectively, act...
Osteocalcin (OC) is a calcium binding protein expressed in mature osteoblasts undergoing mineralization. The OC gene has been identified as target for transcriptional suppression by Msx2, homeodomain transcription factor that controls ossification calvarial bone of the developing skull. We have initiated systematic structure−function analyses using promoter (luciferase reporter) MC3T3-E1 an assay. Msx2 variants were epitope ("FLAG")-tagged monitoring expression Western blot analysis....
FATP4 (fatty acid transport protein 4; also known as SLC27A4) is the most widely expressed member of a family six long chain fatty transporters. highly in enterocytes and has therefore been proposed to be major importer dietary acids. Two independent mutations Fatp4 cause mice born with thick, tight, shiny, "wrinkle-free" skin defective barrier; they die within hours birth from dehydration restricted movements. In contrast, induced keratinocyte-specific deficiency adult causes only mild...
apobec-1 complementation factor (ACF) is an hnRNP family member which functions as the obligate RNA binding subunit of core enzyme mediating C-to-U editing nuclear apolipoprotein B (apoB) transcript. ACF binds to both apoB and apobec-1, catalytic cytidine deaminase, then results in site-specific posttranscriptional mRNA. Targeted deletion apobec1 eliminates mRNA but otherwise well tolerated. However, potential targets beyond are unknown. Here we report generating acf knockout mice using...
Quantitative trait mapping identified a locus colocalizing with L-Fabp, encoding liver fatty acid binding protein, as positional candidate for murine gallstone susceptibility. When fed lithogenic diet (LD) 2 weeks, L-Fabp(-/-) mice became hypercholesterolemic increased hepatic VLDL cholesterol secretion. Seventy-five percent of developed solid gallstones compared 6% wild-type an score (3.29 versus 0.62, respectively; P < 0.01). Hepatic free content, biliary secretion, and the saturation...
The tissue-specific sources and regulated production of physiological signals that modulate food intake are incompletely understood. Previous work showed <i>L-Fabp</i><i><sup>−/−</sup></i> mice protected against obesity hepatic steatosis induced by a high-fat diet, findings at odds with an apparent phenotype in distinct line aged mice. Here we show the lean is recapitulated aged, chow-fed correlates alterations hepatic, but not intestinal, fatty acid amide metabolism. exhibited short-term...
Osteocalcin (OC) is a matrix calcium-binding protein expressed in osteoblasts and odontoblasts undergoing mineralization. OC expression up-regulated part by signals initiated basic fibroblast growth factor (FGF2), cyclic AMP or forskolin (FSK), calcitriol via defined elements DNA-protein interactions the promoter. We identified gene as target for transcriptional suppression Msx2, homeodomain transcription that controls ossification developing skull. In this study, we examine effects of Msx2...
Abstract The RNA-specific cytidine deaminase apobec-1 is an AU-rich RNA binding protein that binds the 3′ untranslated region (UTR) of cyclooxygenase-2 (Cox-2) mRNA and stabilizes its turnover in vitro. Cox-2 overexpression accompanies intestinal adenoma formation both humans mice. Evidence from genetic deletion studies as well pharmacologic inhibition has implicated development adenomas experimental animals colorectal cancer humans. Here, we show small dramatically reduced compound Apcmin/+...
Blocking hepatic very low‐density lipoprotein secretion through genetic or pharmacologic inhibition of microsomal triglyceride transfer protein (Mttp) causes steatosis, yet the risks for developing fibrosis are poorly understood. We report that liver‐specific Mttp knockout mice (Mttp‐LKO) exhibit both steatosis and fibrosis, which is exacerbated by a high‐transfat/fructose diet. When crossed into germline liver fatty acid (FA) binding null (Mttp‐LKO, i.e., double mice) was greatly diminished...
Obesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, gut microbes. Animal studies have identified roles for each of these, however contribution(s) specifically attributed to microbiota remain unclear, as used combinations genetically altered mice, high fat and/or colonization germ-free which an underdeveloped immune system. We investigated role(s) driving obesity inflammation independent manipulations in...