A5103260758- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Muscle metabolism and nutrition
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Peroxisome Proliferator-Activated Receptors
- Regulation of Appetite and Obesity
- Diet, Metabolism, and Disease
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Biochemical Acid Research Studies
- Metabolism and Genetic Disorders
- Muscle Physiology and Disorders
- Fatty Acid Research and Health
- Genetics and Physical Performance
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Sirtuins and Resveratrol in Medicine
- Biochemical effects in animals
- Biochemical Analysis and Sensing Techniques
- Endoplasmic Reticulum Stress and Disease
- Sports Performance and Training
- Neurobiology and Insect Physiology Research
Garvan Institute of Medical Research
2013-2024
The University of Sydney
1997-2024
UNSW Sydney
2008-2023
St Vincent's Clinic
2005-2023
Harry Perkins Institute of Medical Research
2016-2023
Deakin University
2002-2023
Macquarie University
2023
St Vincent's Hospital Sydney
2000-2017
St Vincent's Hospital
2004-2012
Robert Bosch (India)
2012
Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking activation of receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism which mediate this effect, rats were infused with either a lipid emulsion (consisting mostly 18:2 acids) or glycerol. Intracellular C18:2 CoA increased time-dependent fashion, reaching an ∼6-fold elevation 5 h, whereas there was no change concentration any other...
A reduced capacity for mitochondrial fatty acid oxidation in skeletal muscle has been proposed as a major factor leading to the accumulation of intramuscular lipids and their subsequent deleterious effects on insulin action. Here, we examine markers oxidative rodent models resistance associated with an oversupply lipids. C57BL/6J mice were fed high-fat diet either 5 or 20 weeks. Several measured, including (14)C-palmitate oxidation, palmitoyl-CoA isolated mitochondria, enzyme activity...
OBJECTIVE—Berberine (BBR) activates AMP-activated protein kinase (AMPK) and improves insulin sensitivity in rodent models of resistance. We investigated the mechanism activation AMPK by BBR explored whether derivatization could improve its vivo efficacy. RESEARCH DESIGN AND METHODS—AMPK phosphorylation was examined L6 myotubes LKB1−/− cells, with or without Ca2+/calmodulin-dependent (CAMKK) inhibitor STO-609. Oxygen consumption measured isolated muscle mitochondria. The effect a derivative,...
To elucidate cellular mechanisms of insulin resistance induced by excess dietary fat, we studied conscious chronically high-fat–fed (HFF) and control chow diet-fed rats during euglycemic-hyperinsulinemic (560 pmol/1 plasma insulin) clamps. Compared with diet feeding, fat feeding significantly impaired action (reduced whole body glucose disposal rate, reduced skeletal muscle metabolism, decreased suppressibility hepatic production [HGP]). In HFF rats, hyperinsulinemia suppressed circulating...
Skeletal muscle insulin resistance is associated with lipid accumulation, but whether due to reduced or enhanced flux of long-chain fatty acids into the mitochondria both controversial and unclear. We hypothesized that skeletal muscle-specific overexpression isoform carnitine palmitoyltransferase 1 (CPT1), enzyme controls entry acyl CoA mitochondria, would enhance rates acid oxidation improve action in high-fat diet insulin-resistant rats.Rats were fed a standard (chow) for 4 weeks. After 3...
A common nonsense polymorphism (R577X) in the ACTN3 gene results complete deficiency of fast skeletal muscle fiber protein α-actinin-3 an estimated one billion humans worldwide. The XX null genotype is under-represented elite sprint athletes, associated with reduced strength and performance non-athletes, over-represented endurance suggesting that increases at cost power generation. Here we report from Actn3 knockout mice displays force generation, consistent human association studies....
Peroxisome proliferator—activated receptor (PPAR)-α agonists lower circulating lipids, but the consequences for muscle lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-αactivation improves in insulin-resistant rats compared effects with PPAR-γ activation. Three-week high fat-fed male Wistar were untreated or treated specific PPAR-α agonist WY14643 pioglitazone (both 3 mg · kg-1· day-1) last 2 weeks of high-fat feeding. Like pioglitazone, lowered basal...
Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on action insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate was enhanced (50%)...
Long-chain acyl-CoAs (LCACoA) are an activated lipid species that key metabolites in metabolism; they also have a role the regulation of other cellular processes. However, few studies linked LCACoA content rat and human muscle to changes nutritional status insulin action. Fasting rats for 18 h significantly elevated three major ( P < 0.001), whereas high-fat feeding with safflower oil (18:2) diet produced resistance increased total 0.0001) by specifically increasing 18:2-CoA. The red from...
Abstract We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) concentration, acid transporter protein and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of fat, maximum pulmonary O2 uptake; nine well-trained athletes (TRAINED); four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were...
Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, osteocalcin synthesis. Osteocalcin an osteoblast-specific peptide that reported to be involved in normal murine fuel metabolism. We now demonstrate osteoblasts play a pivotal role glucocorticoid-induced dysmetabolism. Osteoblast-targeted...
Flux through the tricarboxylic acid cycle was calculated from oxygen consumption in hearts perfused near physiological work load. Activities of citrate synthase, 2-oxoglutarate dehydrogenase and succinate were measured same hearts. Only activities correlated with fluxes cycle.
α-Actinin-3 deficiency occurs in approximately 16% of the global population due to homozygosity for a common nonsense polymorphism ACTN3 gene. Loss α-actinin-3 is associated with reduced power and enhanced endurance capacity elite athletes nonathletes "slowing" metabolic physiological properties fast fibers. Here, we have shown that results increased calcineurin activity mouse human skeletal muscle adaptive response training. α-Actinin-2, which differentially expressed α-actinin-3-deficient...