A5051881000- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Protein Structure and Dynamics
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- Adipose Tissue and Metabolism
- Food Chemistry and Fat Analysis
- Steroid Chemistry and Biochemistry
- Proteins in Food Systems
- Aquaculture disease management and microbiota
- Drug Transport and Resistance Mechanisms
- Vibrio bacteria research studies
- Lipoproteins and Cardiovascular Health
- ATP Synthase and ATPases Research
- Diet, Metabolism, and Disease
- Lipid metabolism and disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Pregnancy-related medical research
- Muscle Physiology and Disorders
- Sphingolipid Metabolism and Signaling
The University of Texas Southwestern Medical Center
2014-2024
HumanN (United States)
2018-2020
Southwestern Medical Center
2014-2019
Southwestern University
2018
Building Bridges
2016
Center for Human Genetics
2015
Boston University
2008-2014
Boston Medical Center
2009
University Medical Center
2009
KRAS is one of the most commonly mutated oncogenes in human cancer. Mutant aberrantly regulates metabolic networks. However, contribution cellular metabolism to mutant tumorigenesis not completely understood. We report that intracellular fatty acid through Acyl-coenzyme A (CoA) synthetase long-chain family member 3 (ACSL3), which converts acids into Acyl-CoA esters, substrates for lipid synthesis and β-oxidation. ACSL3 suppression associated with depletion ATP causes death lung cancer cells....
Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling isotopomer analysis to trace sterol flux through two in mice. Surprisingly, no tissue canonical K–R pathway. Rather, a hybrid pathway was identified that call modified (MK–R) Proportional varied from 8% preputial gland 97% testes, tissue-specificity observed vivo retained cultured cells. The distribution of isotopomers plasma mirrored liver. Sterol depletion cells...
ABCG5 (G5) and ABCG8 (G8) form a sterol transporter that acts in liver intestine to prevent accumulation of dietary sterols. Mutations either G5 or G8 cause sitosterolemia, recessive disorder characterized by premature coronary atherosclerosis. Hepatic G5G8 mediates cholesterol excretion into bile, but the function relative importance intestinal has not been defined. To determine role G5G8, we developed liver-specific (L-G5G8(-/-)), intestine-specific (I-G5G8(-/-)), total (G5G8(-/-)) KO...
The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 SRC-2), upregulate SP-A transcription, process. As lacking both SRC-1 SRC-2...
Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation long-chain acids. Our previous in vitro studies suggested ELOVL6 elongated saturated acids monounsaturated with lengths 12 to 16 carbons. Here, we describe generation phenotypic characterization Elovl6(-/-) mice. As predicted from studies, livers mice accumulated palmitic (C16:0) palmitoleic (C16:1, n-7)...
An unbiased sample preparation free of interferents (i.e., competing analytes, detergents, plastics) is critical to any lipid MS workflow. Here we present a novel three-phase extraction (3PLE) technique using single-step liquid-liquid (LLE) that allows both and fractionation lipids by polarity. 3PLE composed one aqueous two organic phases. The upper phase enriched in neutral (triacylglycerols cholesteryl esters), while the middle contains major glycerophospholipids. Thin-layer...
Genetic variants that increase the risk of fatty liver disease and cirrhosis have recently been identified in proximity membrane-bound O-acyltransferase domain-containing 7 (MBOAT7). To elucidate link between these disease, we characterized Mboat7 liver-specific KO mice (Mboat7 LSKO). Chow-fed LSKO developed livers associated injury. Lipidomic analysis using MS revealed a pronounced reduction 20-carbon PUFA content phosphatidylinositols (PIs) but not other phospholipids. The change acid...
Accumulation of sterols in endoplasmic reticulum membranes stimulates the ubiquitination 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which catalyzes a rate-limiting step synthesis cholesterol. This marks HMGCR for proteasome-mediated degradation and constitutes one several mechanisms feedback control cholesterol synthesis. Mechanisms sterol-accelerated have been elucidated through study cultured mammalian cells. However, extent to these reactions modulate contribute metabolism...
Dysregulated lipid and glucose metabolism in clear cell renal carcinoma (ccRCC) has been implicated disease progression, whole tumor tissue-based assessment of these changes is challenged by the heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations tumor.We applied Dixon-based for vivo quantification accumulation (fat fraction [FF]) targeted regions interest 45 primary ccRCCs correlated measures to mass spectrometry-based lipidomics metabolomics...
Phospholipid monolayers play a critical role in the structure and stabilization of biological interfaces, including all membranes, alveoli lungs, fat droplets adipose tissue, lipoproteins. The behavior phospholipids bilayers at an air−water interface is well understood. However, study oil−water interfaces limited due to technical challenges. In this study, egg phosphatidylcholine (EPC) was deposited from small unilamellar vesicles onto bubble either air or triolein (TO) formed low-salt...
TASIN (Truncated APC-Selective Inhibitors) compounds are selectively toxic to colorectal cancer cells with APC mutations, although their mechanism of action remains unknown. Here, we found that TASINs inhibit three enzymes in the postsqualene cholesterol biosynthetic pathway including EBP, DHCR7, and DHCR24. Even though all these required for biosynthesis, only inhibition most upstream enzyme, led cell death via depletion downstream sterols, an observation was confirmed by genetic silencing...
Abstract De novo lipogenesis (DNL) is disrupted in a wide range of human disease. Thus, quantification DNL may provide insight into mechanisms and guide interventions if it can be performed rapidly noninvasively. flux commonly measured by 2 H incorporation fatty acids following deuterated water ( O) administration. However, the sensitivity this approach limited natural abundance 13 C, which masks detection mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography...
HNF-1 β is a tissue–specific transcription factor that expressed in the kidney and other epithelial organs. Humans with mutations HNF-1β develop cysts, regulates of several cystic disease genes. However, complete spectrum –regulated genes pathways not known. Here, using chromatin immunoprecipitation/next generation sequencing gene expression profiling, we identified 1545 protein-coding are directly regulated by murine cells. Pathway analysis predicted cholesterol metabolism. Expression...
Pathogens find diverse niches for survival including inside a host cell where replication occurs in relatively protective environment. Vibrio parahaemolyticus is facultative intracellular pathogen that uses its type 3 secretion system 2 (T3SS2) to invade and replicate cells. Analysis of the T3SS2 pathogenicity island encoding appeared lack mechanism egress this bacterium from invaded cell. Using combination molecular tools, we found VPA0226, constitutively secreted lipase, required escape V....
Loss of dysferlin (DYSF) protein in humans results limb-girdle muscular dystrophy 2B, characterized by progressive loss muscles the distal limbs with impaired locomotion. The DYSF-null (Bla/J) mouse develops severe steatotic upon aging. Here, we report a marked increase adipocytes, especially psoas and gluteus but not soleus tibialis anterior aged Bla/J mice compared WT mice. There was robust upregulation mRNA expression enzymes involved lipogenesis triacylglycerol (TAG) synthesis pathways...
Amphipathic α-helices (AαH) are the primary structural motif of exchangeable apolipoproteins. AαHs in apolipoproteins adsorb, remodel, and desorb at surface plasma lipoproteins response to changes their size or composition. A triolein/water (TO/W) interface was used as a model study adsorption desorption lipoprotein-like interface. We previously reported that AαH peptides spontaneously adsorb TO/W interface, but they only partially from when excess peptide removed system. This finding...
ApolipoproteinB (ApoB) is a lipid binding protein that nonexchangeable component of chylomicrons, VLDL, and LDL. In the liver intestinal cells ApoB recruits to form nascent triacylglycerol rich particles cotranslationally in endoplasmic reticulum membrane which are then processed secreted plasma lipoproteins. The N-terminal domain, comprises first 22% apoB, controlled manner. 6% (residues 1-291) N-terminus does not bind lipid. including residues 292-782 (B6-17), forms pocket predicted...