A5018868576- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Obesity, Physical Activity, Diet
- NF-κB Signaling Pathways
- Gestational Diabetes Research and Management
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Cellular Mechanics and Interactions
- Genetic Syndromes and Imprinting
- Regulation of Appetite and Obesity
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Melanoma and MAPK Pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiomyopathy and Myosin Studies
- Cancer, Hypoxia, and Metabolism
- Fatty Acid Research and Health
- Pregnancy and preeclampsia studies
- Cardiovascular and Diving-Related Complications
University of Oregon
2013-2023
University of California, San Diego
2009-2012
Maternal obesity is proposed to alter the programming of metabolic systems in offspring, increasing risk for developing diseases; however, cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model examine impact maternal Western-style diet (WSD) alone, or combination with (Ob/WSD), on fetal skeletal muscle metabolism studied early third trimester. We find that responds Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and switches...
Significance The nuclear factor kappa B (NF-κB) family of transcription factors regulates hundreds genes in response to stress. Stress responses must be robust when needed and then completely rapidly turned off. A inhibitor proteins, the IκBs, is responsible for turning off NF-κBs. Our study shows that IκBα turns NF-κB(RelA/p50) by binding DNA-bound NF-κB, forming a transient ternary complex. complex lasts only milliseconds before DNA dissociates from resulting IκBα–NF-κB extremely stable...
Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass and insulin resistance, suggesting may be restricted molecular events that occur during fetal development. To explore the basis of growth, we used a sheep model progressive placental insufficiency-induced IUGR to assess myoblast proliferation within intact skeletal vivo isolated myoblasts stimulated with vitro Gastrocnemius soleus weights reduced 25% fetuses compared those controls (CON)....
Infants born to mothers with obesity have a greater risk for childhood and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used Japanese macaque model investigate whether maternal combined Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed control or WSD prior during pregnancy through lactation, subsequently weaned WSD. Muscle glucose uptake signaling measured ex vivo in fetal (n = 5–8/group) juvenile...
Maternal consumption of a Western-style diet (mWD) during pregnancy alters fatty acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact these adaptations the pathways underlying disordered lipid are incompletely understood. Therefore, we tested whether mWD chronically fed to lean, insulin-sensitive adult Japanese macaques throughout lactation would muscle oxidative capacity adolescent offspring postweaning (pw) (WD) or control (CD). Although body...
Recognition of stop codons by class I release factors is a fundamental step in the termination phase protein synthesis. Since premature costly to cell, have efficiently discriminate between and sense codons. To understand mechanism discrimination codons, we developed new, pre-steady state kinetic assay monitor interaction RF1 with ribosome. Our results show that associates similar association rate constants ribosomes programmed or However, dissociation from as much 3 orders magnitude faster...
The selection of aminoacyl-tRNAs by the ribosome is a fundamental step in elongation cycle protein synthesis. tRNA multistep process that ensures only correct are accepted while incorrect rejected. A key formation base pairs between anticodon aminoacyl-tRNA and mRNA codon site, called "codon recognition". Here, we report development new, fluorescence-based, kinetic assay for monitoring recognition ribosome. Using this assay, show second-order binding under optimal conditions. Additionally,...
While current thinking posits that insulin signaling to glucose transporter 4 (GLUT4) exocytic translocation and uptake in skeletal muscle adipocytes is controlled by phosphorylation-based signaling, many proteins this pathway are acetylated on lysine residues. However, the importance of acetylation acetyltransferases insulin-stimulated incompletely defined. Here, we demonstrate combined loss E1A binding protein p300 (p300) cAMP response element (CBP) mouse caused a complete uptake....
Class I peptide release factors 1 and 2 (RF1 RF2, respectively) recognize the stop codons in ribosomal decoding center catalyze peptidyl-tRNA hydrolysis. High-fidelity codon recognition by these is essential for accurate synthesis ribosome recycling. X-ray crystal structures of RF1 RF2 bound to have identified residues mRNA-protein interface that appear be critical recognition. Especially interesting a conserved histidine all bacterial class forms stacking interaction with second base codon....
Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding (CBP) are phosphorylated activated by Akt, p300/CBP can acetylate inactivate thus giving rise to possible Akt-p300/CBP axis. Our objective was determine the importance CBP muscle insulin sensitivity. We used Cre-LoxP methodology generate mice with germline [muscle creatine kinase promoter (P-MCK C-MCK)] or inducible...
Introduction: The Phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in skeletal muscle insulin-stimulated glucose uptake. While whole-body and tissue specific knockout (KO) of individual or combinations the regulatory subunits PI3K (p85α, p55α p50α p85β); increase insulin sensitivity, no study has examined whether increasing expression would inhibit action vivo. Therefore, objective this was to determine muscle-specific overexpression subunit impairs prevents its...
Signal transducer and activator of transcription 3 (STAT3) was recently found to be localized mitochondria in a number tissues cell types, where it modulates oxidative phosphorylation via interactions with the electron transport proteins, complex I II. Skeletal muscle is densely populated although whether STAT3 contributes skeletal capacity unknown. In present study, we sought elucidate contribution mitochondrial function by studying mice muscle-specific knockout (mKO). First, developed...
Early-life exposure to maternal obesity or a calorically dense Western-style diet (WSD) is strongly associated with greater risk of metabolic diseases in offspring, most notably insulin resistance and dysfunction-associated steatotic liver disease (MASLD). Prior studies our well-characterized Japanese macaque model demonstrated that offspring dams fed WSD, even when weaned onto control (CTR) diet, had reductions skeletal muscle mitochondrial metabolism increased compared on CTR diet. In the...
Whether the histone deacetylase (HDAC) and sirtuin families of protein deacetylases regulate insulin-stimulated glucose uptake, independent their transcriptional effects, has not been studied. Our objective was to determine nontranscriptional role HDACs sirtuins in regulation skeletal muscle insulin action. Basal uptake signaling acetylation were assessed L6 myotubes from C57BL/6J mice that treated acutely (1 h) with HDAC (trichostatin A, panobinostat, TMP195) inhibitors (nicotinamide)....
Intrauterine growth restricted (IUGR) fetuses are born with lower skeletal muscle mass, fewer proliferating myoblasts, and myofibers compared to normally growing fetuses. Plasma concentrations of insulin, a myogenic factor, in IUGR We hypothesized that two-week insulin infusion at 75% gestation would increase myoblast proliferation fiber number fetal sheep. Catheterized control received saline (CON-S, n=6), the either (IUGR-S, n=7) or (IUGR-I, 0.014 ± 0.001 units/kg/hr, n=11) for 14 days....
IGF-1 is a critical fetal growth-promoting hormone. Experimental infusion of an analog, human recombinant LR3 IGF-1, into late gestation sheep increased organ growth and skeletal muscle myoblast proliferation. However, has low affinity for IGF binding proteins (IGFBP), thus reducing physiologic regulation bioavailability. The peptide sequences also differ. To overcome these limitations with we developed ovine (sheep) specific (oIGF-1) tested its effect on in sheep. First, measured vitro...
Infants born to mothers with obesity have a greater risk for childhood and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used Japanese macaque model investigate whether maternal combined western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed control or WSD prior during pregnancy through lactation, subsequently weaned WSD. Muscle glucose uptake signaling measured ex vivo in fetal (n=5-8/group) juvenile...
Adult offspring of insulin resistant mothers show increased susceptibility to type 2 diabetes and obesity. Previous studies in this population have found reduced mitochondrial function decreased lipid oxidation skeletal muscle consistent with resistance. It is not known how maternal diet affects functioning the individual electron transport chain complexes. We were specifically interested investigating whether exposure western style (WSD), or post‐weaning (PW) WSD, would impact Complex IV...
Insulin resistance (IR), a metabolic feature of obesity, drives number diseases. Recently, the focus obesity research has been adipocyte‐immune cell crosstalk and its influence on systemic insulin sensitivity (IS). Currently, induced IR is thought to arise secondary inflammation due infiltration adipose tissue (AT) with pro‐inflammatory immune cells. Obesity progressive disease, alterations in AT following acute nutrient excess, prior development are not well understood. Phosphotidylinositol...
<p dir="ltr">Maternal (m) consumption of a Western-style diet (WD) during pregnancy alters fatty-acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact these adaptations the pathways underlying disordered lipid are incompletely understood. Therefore, we tested whether mWD chronically fed to lean, sensitive adult Japanese macaques throughout lactation would muscle oxidative capacity adolescent offspring postweaning (pw)WD or control (CD). Although...
<p dir="ltr">Maternal (m) consumption of a Western-style diet (WD) during pregnancy alters fatty-acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact these adaptations the pathways underlying disordered lipid are incompletely understood. Therefore, we tested whether mWD chronically fed to lean, sensitive adult Japanese macaques throughout lactation would muscle oxidative capacity adolescent offspring postweaning (pw)WD or control (CD). Although...