A5000180771- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- Metabolism and Genetic Disorders
- Hepatitis C virus research
- Exercise and Physiological Responses
- Cardiovascular and exercise physiology
- Muscle metabolism and nutrition
- Endoplasmic Reticulum Stress and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Peroxisome Proliferator-Activated Receptors
- Nutrition and Health in Aging
- Hepatitis B Virus Studies
- Biochemical effects in animals
- Dietary Effects on Health
- Regulation of Appetite and Obesity
- Pancreatic function and diabetes
- Spinal Cord Injury Research
- Thermal Regulation in Medicine
- Ubiquitin and proteasome pathways
- Thermoregulation and physiological responses
- HIV Research and Treatment
University of Kansas Medical Center
2016-2025
Veterans Health Administration
2018-2023
Center for Children
2020-2023
University of Kansas
2022-2023
Kansas Health Institute
2022
Children's Mercy Hospital
2022
Kansas City VA Medical Center
2018-2019
University of California, Davis
2013-2016
Agricultural Research Service
2014
University of California System
2014
Incomplete β-oxidation of fatty acids in mitochondria is a feature insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations medium- long-chain acylcarnitines (by-products incomplete β-oxidation) are elevated T2DM resistance. In previous study, we reported mixed d,l isomers C12- or C14-carnitine induced an NF-κB-luciferase reporter gene RAW 264.7 cells, suggesting potential activation proinflammatory pathways. Here, determined whether the...
Insulin resistance may be linked to incomplete fatty acid β-oxidation and the subsequent increase in acylcarnitine species different tissues including skeletal muscle. It is not known if acylcarnitines participate muscle insulin or simply reflect dysregulated metabolism. The aims of this study were determine whether can elicit better understand link between β-oxidation, oxidative stress, inflammation, insulin-resistance development. Differentiated C2C12, primary mouse, human myotubes treated...
In this study, we explored the roles of microRNAs in adipocyte differentiation and metabolism. We first knocked down Argonaute2 (Ago2), a key enzyme processing micro-RNAs (miRNAs), to investigate potential role for miRNAs and/or Although did not observe dramatic differences adipogenesis between Ago2 knock-down control 3T3-L1 cells, incorporation [(14)C]glucose or acetate into triacylglycerol, steady-state levels triacyglycerol were all reduced, suggesting To study specific biology, screened...
The extracellular matrix (ECM) plays an important role in the maintenance of white adipose tissue (WAT) architecture and function, proper ECM remodeling is critical to support WAT malleability accommodate changes energy storage needs. Obesity adipocyte hypertrophy place a strain on machinery, which may promote disordered altered integrity could proinflammatory cell stress signals. To explore these questions, new methods were developed quantify omental subcutaneous tensile strength collagen...
Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests VMP1 plays a critical role in lipoprotein secretion zebra fish cultured cells. However, pathophysiological roles mechanisms by which accumulation non-alcoholic fatty liver disease (NAFLD) steatohepatitis (NASH) are unknown.Liver-specific hepatocyte-specific Vmp1 knockout mice as well knock-in were generated crossing...
Acylcarnitines, important lipid biomarkers reflective of acyl-CoA status, are metabolites that possess bioactive and inflammatory properties. This study examined the potential for long-chain acylcarnitines to activate cellular inflammatory, stress, death pathways in a skeletal muscle model. Differentiated C2C12 myotubes treated with l-C14, C16, C18, C18:1 carnitine displayed dose-dependent increases IL-6 production concomitant rise markers cell permeability death, which was not observed...
Apolipoprotein E4 (APOE4) is the greatest genetic risk factor for Alzheimer's (AD) and linked to whole-body metabolic dysfunction. However, it's unclear how APOE4 interacts with modifiable factors like diet impact tissues central regulating metabolism. We examined APOE4- Western diet-driven effects in skeletal muscle using APOE3 (control) targeted replacement mice on a C57BL/6NTac background fed high-fat (HFD, 45% kcal fat) or low-fat (LFD, 10% four months (n=7-8 per genotype/diet/sex...
Hepatic mitochondrial adaptations to physical activity may be regulated by biogenesis (PGC1α) and mitophagy (BNIP3). Additionally, these sex-dependent. Chronic increase in lowers basal respiratory capacity mice. Female mice have higher hepatic electron transport system protein content, elevated capacity, lowered mitophagic flux, emit less H
The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator biogenesis, BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), regulator, would (respiratory capacity, H 2 O production, mitophagy) to high-fat diet (HFD) HFD plus via voluntary...
Induction of the chaperone heat shock protein 72 (HSP72) through treatment (HT), exercise, or overexpression improves glucose tolerance and mitochondrial function in skeletal muscle. Less is known about HSP72 liver where lipid accumulation can result insulin resistance nonalcoholic fatty disease (NAFLD). The purpose this study was 1) to determine whether weekly vivo HT induces hepatic rats fed a high-fat diet (HFD) 2) ability protect against dysfunction primary hepatocytes. Male Wistar were...
Heat treatment (HT) effectively prevents insulin resistance and glucose intolerance in rats fed a high-fat diet (HFD). The positive metabolic actions of heat shock protein 72 (HSP72), which include increased oxidative capacity enhanced mitochondrial function, underlie the protective effects HT. purpose this study was to test ability HSP72 induction mitigate consumption short-term 3-day HFD selectively bred be low-capacity runners (LCRs) high-capacity (HCRs)—selective breeding that results...
We recently reported that compared with males, female mice have increased hepatic mitochondrial respiratory capacity and are protected against high-fat diet-induced steatosis. Here, we sought to determine the role of estrogen in function, steatosis, bile acid metabolism investigate potential benefits exercise absence or presence via ovariectomy (OVX). Female C57BL (n = 6 per group) were randomly assigned sham surgery (sham), (OVX), OVX plus estradiol replacement therapy (OVX + Est). Half...
On our initial discovery that prion protein (PrP)-derived peptides were capable of capturing the pathogenic (PrP(Sc)), we have been interested in how these interact with PrP(Sc). After screening from entire human PrP sequence, found two (PrP(19-30) and PrP(100-111)) binding full-length PrP(Sc) plasma, a medium containing complex mixture other proteins including vast excess normal (PrP(C)). The limit detection for captured was calculated to be 8 amol approximately 10(5)-fold dilution 10%...
Broad, multispecific CD4(+) and CD8(+) T-cell responses to the hepatitis C virus (HCV), as well virus-cross-neutralizing antibodies, are associated with recovery from acute infection may also be in chronic HCV patients a favorable response antiviral treatment. In order recapitulate all of these an ideal vaccine regimen, we have explored use recombinant polypeptides combined various Th1-type adjuvants replication-defective alphaviral particles encoding proteins prime/boost modalities BALB/c...
The aim of this study was to test whether increased energy expenditure (EE), independent physical activity, reduces acute diet-induced weight gain through tighter coupling intake demand and enhanced metabolic adaptations.Indirect calorimetry quantitative magnetic resonance imaging were used assess metabolism body composition during 7-day high-fat/high-sucrose (HFHS) feeding in male female mice housed at divergent temperatures (20°C vs. 30°C).As previously observed, 30°C housing resulted...
Low intrinsic aerobic capacity is associated with increased all-cause and liver-related mortality in humans. the low runner (LCR) rat increases susceptibility to acute chronic high-fat/high-sucrose diet-induced steatosis, without observed liver inflammation. Addition of excess cholesterol a diet produced greater steatosis LCR high (HCR) rats. However, demonstrated inflammatory apoptotic markers compared HCR rat. The progressive non-alcoholic fatty disease rats following western feeding was...
New Findings What is the central question of this study? Do peripheral sensory neurons metabolize fat‐based fuel sources, and does a ketogenic diet modify these processes? main finding its importance We show that axons from mice fed respond to sources with reduced respiration H 2 O emission compared control diet. These results add our understanding responses neuropathy associated poor diet, obesity metabolic syndrome. findings should be incorporated into current ideas axonal protection might...
Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study ( n = 50) compared respiratory function gene expression profiling cognitively healthy older adults (CH; 24) to 26 individuals the earliest phase ad-related cognitive decline, mild impairment (MCI; 11) or MCI taking ad medication donepezil (MCI + med; 15). Mitochondrial kinetics were...
Exercise is critical for improving metabolic health and putatively maintains or enhances mitochondrial quality control in tissues. Although previous work has shown that exercise elicits hepatic biogenesis, it unknown if acute activates mitophagy, the selective degradation of damaged low-functioning mitochondria. We tested an bout treadmill running increased mitophagic flux both right after 2-h postexercise 15- to 24-wk-old C57BL/6J female mice. Acute did not significantly increase markers...
ABSTRACT Recent clinical studies suggest that hepatitis B virus (HBV) load and genotype may be independent predictors of responses to antiviral therapies. However, it is difficult for clinicians accurately determine viral loads in patient samples because results—both the values units measure—can vary greatly among different tests. Accordingly, World Health Organization (WHO) has produced first international standard HBV DNA nucleic acid amplification technology (NAT) assays. In present...
Both lipid oversupply and poor mitochondrial function (low respiration elevated H2O2 emission) have been implicated in the development of hepatic steatosis liver injury. Mitophagy, targeted degradation low-functioning mitochondria, is critical for maintaining quality control. Here, we used intralipid injection combined with acute (4 day) chronic (4-7wk) high-fat diets (HFD) to examine whether would decrease emission increase overload. We tested these effects male female wild type (WT) mice...
Excessive cellular accumulation or exposure to lipids such as long-chain acylcarnitines (LCACs), ceramides, and others is implicated in cell stress inflammation. Such a situation might manifest when there significant mismatch between fatty acid (LCFA) availability versus storage oxidative utilization; for example, cardiac ischemia, increased LCACs may contribute tissue infarct damage. Perturbed LCFAβ-oxidation also seen oxidation disorders (FAODs). FAODs typically with fasting-...