A5076016752- Cholesterol and Lipid Metabolism
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Sphingolipid Metabolism and Signaling
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Dietary Effects on Health
- Diabetes Treatment and Management
- Alcohol Consumption and Health Effects
- Bone and Dental Protein Studies
- Cellular transport and secretion
- Diet and metabolism studies
- Turfgrass Adaptation and Management
- Salivary Gland Disorders and Functions
- Lipid metabolism and disorders
- Erythrocyte Function and Pathophysiology
- Cardiovascular Disease and Adiposity
- Lysosomal Storage Disorders Research
- Thermoregulation and physiological responses
National Institute of Diabetes and Digestive and Kidney Diseases
2017-2023
National Institutes of Health
2017-2023
University of Maryland, Baltimore
2013-2023
Wake Forest University
2006-2021
University of Maryland, College Park
2013-2021
Nanjing Forestry University
2019
China Three Gorges University
2013
SUNY Downstate Health Sciences University
2013
Icahn School of Medicine at Mount Sinai
2008-2009
Niemann-Pick C1-like 1 (NPC1L1) is required for cholesterol absorption. Intestinal NPC1L1 appears to be a target of ezetimibe, absorption inhibitor that effectively lowers plasma LDL-cholesterol in humans. However, human liver also expresses NPC1L1. Hepatic function was previously unknown, but we recently discovered localizes the canalicular membrane primate hepatocytes and facilitates uptake hepatoma cells. Based upon these findings, hypothesized hepatic allows retention biliary by...
Although NPC1L1 is required for intestinal cholesterol absorption, data demonstrating mechanisms by which this protein facilitates the process are few. In study, a hepatoma cell line stably expressing human was established, and uptake studied. A relationship between intracellular trafficking apparent. At steady state, proteins localized predominantly to transferrin-positive endocytic recycling compartment, where free also accumulated as revealed filipin staining. Interestingly, acute...
Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) inhibit expression adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted ∼80-95% knockdown protein both liver white adipose tissue. In chow-fed mice, ASO-mediated...
How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of α/β-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator also known as comparative gene identification 58 (CGI-58), promotes this metabolic and enhances malignancies colorectal carcinomas (CRCs). Silencing Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout Apc(Min/+) mice robustly increases tumorigenesis transformation...
Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific knockout (MaKO) mice aggravates HFD-induced glucose intolerance which is associated with augmented systemic/tissue inflammation activation of adipose tissue...
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering metabolism other tissues. To directly address this...
Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal absorption of dietary and biliary cholesterol. Ezetimibe, by inhibiting NPC1L1 function, is widely used to treat hypercholesterolemia in humans. Interestingly, ezetimibe treatment appears attenuate hepatic steatosis rodents humans without a defined mechanism. Overconsumption high-fat diet (HFD) represents major cause metabolic disorders including fatty liver. To determine whether how deficiency prevents HFD-induced steatosis, this study, we...
Alcohol-associated liver disease (ALD) pathologies include steatosis, inflammation, and injury, which may progress to fibrosis, cirrhosis, cancer. The receives ~60% of fatty acids from adipose tissue triglyceride hydrolysis, but the role this lipolytic pathway in ALD development has not been directly examined any genetic animal models with selective inactivation lipolysis.
Abstract We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal absorption, reduces the output dry stool in mice. As food intake remains unaltered NPC1L1-knockout (L1-KO) mice, we hypothesized NPC1L1 deficiency may alter gut microbiome to reduce output. Consistently, here demonstrate phyla fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) reduced Inhibition by its...
The normalization of data by choosing suitable reference genes is fundamental for obtaining accurate and reliable results in quantitative real-time polymerase chain reaction (qPCR) analyses. In this study, the expression stability 12 candidate Pinus massoniana under different abiotic stresses was evaluated using four statistical algorithms: geNorm, NormFinder, BestKeeper, RefFinder. indicate that following could be used as treatments: Actin 2 (ACT2) F-box family gene (F-box) salinity...
Mice lacking Niemann-Pick C1-Like 1 (NPC1L1) (NPC1L1−/−mice) exhibit a defect in intestinal absorption of cholesterol and phytosterols. However, wild-type (WT) mice do not efficiently absorb accumulate phytosterols either. Cell-based studies show that NPC1L1 is much weaker transporter for than cholesterol. In this study, we examined the role phytosterol trafficking ATP-binding cassette (ABC) transporters G5 G8 (G5/G8−/− mice). G5/G8−/− develop sitosterolemia, genetic disorder characterized...
Objectives— Activation of liver x receptor (LXR) raises plasma HDL-cholesterol (HDL-C) in mice. Interestingly, the LXR agonist GW3965 fails to raise HDL-C mice lacking intestinal ABCA1, indicating that ABCA1 plays a predominant role GW3965-mediated HDL production. How this is coupled function remains elusive. Because cholesterol essential for assembly and directly regulates expression via activating LXR, we hypothesized absorption, major intestine, modulates LXR-dependent formation. Methods...
Abstract Humans and rodents with Comparative Gene Identification-58 (CGI-58) mutations manifest nonalcoholic fatty liver disease (NAFLD). Here we show that CGI-58 knockout (LivKO) mice fed a Western diet rapidly develop advanced NAFLD, including steatohepatitis (NASH) hepatic fibrosis. After 14 weeks of challenge, starting at 6 age, LivKO showed increased inflammatory cell infiltration proinflammatory gene expression in the liver, which was associated elevated plasma levels...
Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective this study was to examine modulating macrophage RCT Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1(LivOnly)) mice, an animal model that is defective both and intestinal absorption, determine whether NPC1L1 inhibitor ezetimibe facilitates by inhibiting hepatic NPC1L1.L1(LivOnly) mice were generated crossing knockout (L1-KO) with...
Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations human CGI-58 cause TG accumulation numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but fatty meal does induce temporary cytosolic of LDs. Accumulated LDs eventually cleared out, implying existence hydrolytic machinery enterocytes. However, identities proteins responsible for LD-TG remain unknown....
Diosgenin exists in some food supplements and herbal medicines lowers plasma cholesterol by increasing fecal excretion. It is believed that diosgenin promotes excretion stimulating biliary secretion decreasing intestinal absorption. Niemann-Pick C1-like 1 (NPC1L1) was recently identified as an essential protein for To determine the relative contribution of absorption diosgenin-stimulated excretion, wild-type (WT) NPC1L1-knockout (L1KO) mice were fed a diet with or without 1% diosgenin. Fecal...
Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal cholesterol absorption. NPC1L1 knockout (L1-KO) mice were recently shown to be resistant high-fat diet (HFD)-induced obesity in one study, which was contrary several other studies. Careful comparison of dietary compositions these studies implies a potential role regulating weight gain. To examine this potential, wild-type (WT) and L1-KO fed three sets diets for various durations: (1) HFD without added 5 weeks; (2) high-carbohydrate with or...
Intramyocellular accumulation of lipids is often associated with insulin resistance. Deficiency comparative gene identification-58 (CGI-58) causes cytosolic deposition triglyceride (TG)-rich lipid droplets in most cell types, including muscle due to defective TG hydrolysis. It was unclear, however, whether CGI-58 deficiency-induced influences sensitivity. Here we show that muscle-specific knockout mice relative their controls have increased glucose tolerance and sensitivity on a Western-type...