- Adipose Tissue and Metabolism
- Cardiovascular and exercise physiology
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Alzheimer's disease research and treatments
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Extracellular vesicles in disease
- Sleep and related disorders
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Circadian rhythm and melatonin
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- Cardiovascular Effects of Exercise
- Lipid metabolism and biosynthesis
- Muscle Physiology and Disorders
- Regulation of Appetite and Obesity
- Sleep and Wakefulness Research
- Advanced MRI Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Cardiovascular Function and Risk Factors
- Pharmacology and Obesity Treatment
- Thermoregulation and physiological responses
- Amyloidosis: Diagnosis, Treatment, Outcomes
Deakin University
2013-2024
Australian Regenerative Medicine Institute
2022-2023
Monash University
2022-2023
Victoria University
2015-2022
University of Virginia
2013
University of Tasmania
2010-2011
University of Virginia Health System
2011
Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function thought be central Mitochondrial dysfunction reduced secretion are also observed in β-cells of humans the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions chromosome 21 that may perturbed glucose homeostasis we profiled glycaemic status different DS mouse models. The...
Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Because exercise improves tolerance function, alters rhythms, we investigated whether may counteract effects induced by inadequate sleep. To minimize between-group differences baseline characteristics, 24 healthy young males were allocated into one three...
Non-alcoholic fatty liver disease (NAFLD) is prevalent in the majority of obese individuals, but a subset, this progresses to non-alcoholic steatohepatitis (NASH) and fibrosis. The mechanisms that prevent NASH fibrosis NAFLD patients remain unclear. Here we report NAD(P)H oxidase (NOX)-4 nuclear factor erythroid 2-related 2 (NFE2L2) were elevated hepatocytes early progression NASH/fibrosis. Mitochondrial-derived reactive oxygen species (ROS) activated NFE2L2 induce expression NOX4, which...
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency AIF known to result defective oxidative phosphorylation (OXPHOS), via loss of complex I activity assembly other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that decrease would chronic disease (CKD). Here, report partial knockdown Aif mice recapitulates many features CKD, association compensatory increase ATP pool...
Exercise stimulates mitochondrial biogenesis and increases respiratory function content. However, during high-intensity exercise muscle pH can decrease below 6.8 with a concomitant increase in lactate concentration. This drop is associated reduced exercise-induced biogenesis, while increased may act as signaling molecule to affect biogenesis. Therefore, this study we wished determine the impact of altering concentration L6 myotubes on genes proteins known be involved We also examined...
Assessments of mitochondrial respiration and content are common in skeletal muscle research exercise science. However, many sources technical biological variation render these analyses susceptible to error. This study aimed better quantify the reliability different experimental designs and/or techniques so as assist researchers obtain more reliable data.We examined repeatability maximal oxidative phosphorylation permeabilized fibres via high-resolution respirometry, citrate synthase activity...
The aetiology of the development type 2 diabetes remains unresolved. In present study, we assessed whether an impairment insulin-mediated microvascular perfusion occurs early in onset insulin resistance.Hooded Wistar rats were fed either a normal diet (ND) or high-fat (HFD) for 4 weeks. Anaesthetized animals subjected to isoglycaemic hyperinsulinaemic clamp (3 10 mU/min/kg x h), and measurements made glucose infusion rate (GIR), hindleg uptake, muscle uptake by 2-deoxy-d-glucose (R'g),...
We examined insulins uptake and transendothelial transport by endothelial cells in order to: (i) ascertain whether insulin accumulates within the to concentrations greater than media; (ii) compare trans that of inulin (using latter as a tracer for passive or leaked); and; (iii) determine transported depended on action.Using 125I-insulin at physiologic we measured both bovine aortic cell volume using tritiated 3-O-methylglucose.Bovine accumulate > five-fold above media insulin, but not...
Abstract There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease Alzheimer’s disease. The role of amyloid beta 42 (Aβ ) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ , which increased from male mice with associated higher plasma . Increasing circulating levels without has no effect on systemic glucose homeostasis but obesity-like effects the heart, including reduced cardiac clearance impaired function....
Autophagy is a key intracellular mechanism by which cells degrade old or dysfunctional proteins and organelles. In skeletal muscle, evidence suggests that exercise increases autophagosome content autophagy flux. However, the exercise-induced response seems to differ between rodents humans, little known about how different prescription parameters may affect these results. The present study utilised muscle samples obtained from four experimental studies using rats humans. Here, we show that,...
There is considerable support for the concept that insulin-mediated increases in microvascular blood flow to muscle impact significantly on glucose uptake. Since with insulin have been shown be nitric oxide-dependent inhibition of cGMP-degrading phosphodiesterases (cGMP PDEs) predicted enhance perfusion and Therefore, we studied effects pan-cGMP PDE inhibitor zaprinast metabolic vascular actions muscle. Hyperinsulinemic euglycemic clamps (3 mU·min(-1)·kg(-1)) were performed anesthetized rats...
The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the beta peptide that is implicated in development Alzheimer's disease. It well established APP via its cleaved regulates aspects neuronal metabolism. Emerging evidence suggests amyloidogenic processing can lead to altered systemic metabolism, similar observed metabolic disease states. In present study, we investigated effect deficiency on obesity-induced...
Insulin-induced microvascular recruitment is important for optimal muscle glucose uptake. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an activator of AMP-activated protein kinase), can also induce recruitment, at doses that do not acutely activate transport in rat muscle. Whether low AICAR augment physiologic insulin action unknown. In the present study we used euglycemic hyperinsulinemic clamp to assess whether augmented by dose AICAR.Anesthetized rats were studied during...
Protein kinase D (PKD) is emerging as an important regulating energy balance and glucose metabolism; however, whether hepatic PKD activity can be targeted to regulate these processes currently unclear. In this study, was reduced using adeno-associated virus vectors express a dominant-negative (DN) version of PKD1, which impairs the action all three isoforms. chow-fed mice, DN expression increased whole-body oxidation, but had only mild effects on insulin tolerance no homeostasis following...
The aim of this study was to investigate the relationship between mitochondrial content and respiratory function whole-body insulin resistance in high-fat diet (HFD) fed rats. Male Wistar rats were given either a chow or an HFD for 12 weeks. After 4 weeks dietary intervention, half each group began 8 interval training. In vivo glucose tolerance assessed. Mitochondrial assessed permeabilised soleus white gastrocnemius (WG) muscles. determined by measurement citrate synthase (CS) activity...
Abstract Background The assessment of mitochondrial respiration and content are two common measurements in the fields skeletal muscle research exercise science. However, to verify validity observed changes both following an intervention such as training, it is important determine reliability reproducibility experimental design and/or techniques employed. We examined repeatability widely used methodologies for assessing content, respectively; measurement maximal oxidative phosphorylation...
Abstract Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Given that exercise improves tolerance, function, alters rhythms, we investigated whether may counteract effects induced by inadequate sleep. We report sleeping 4 hours per night, five nights, reduced with novel observations associated reductions in...
Exercise training can increase both mitochondrial content and respiration. Despite its popularity, high-intensity exercise be accompanied by mild acidosis (also present in certain pathological states), which may limit exercise-induced adaptations to skeletal muscle mitochondria. The aim of this study was determine if administration ammonium chloride (0.05 g/kg) Wistar rats before each individual session (5 sessions/wk for 8 wk) reduced training-induced increases (measured citrate synthase...
Aim Exercise is able to increase both muscle protein synthesis and mitochondrial biogenesis. However, acidosis, which can occur in pathological states as well during high-intensity exercise, decrease function, whilst its impact on disputed. Thus, the aim of this study was determine effect a mild physiological pH, by administration ammonium chloride, myofibrillar synthesis, associated molecular signaling events. Methods Male Wistar rats were given either placebo or chloride prior short...