A5034774668- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular and exercise physiology
- Muscle Physiology and Disorders
- Spinal Fractures and Fixation Techniques
- Nitric Oxide and Endothelin Effects
- Lipid metabolism and biosynthesis
- Crime Patterns and Interventions
- Muscle metabolism and nutrition
- Social Media and Politics
- Spine and Intervertebral Disc Pathology
- Surfactants and Colloidal Systems
- Sphingolipid Metabolism and Signaling
- Diet, Metabolism, and Disease
- Air Traffic Management and Optimization
- Aviation Industry Analysis and Trends
- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Diet and metabolism studies
- Pelvic and Acetabular Injuries
- Environmental Chemistry and Analysis
- Community Health and Development
- Heart Rate Variability and Autonomic Control
Australasian College for Emergency Medicine
2021
Royal National Orthopaedic Hospital NHS Trust
2004-2020
University College London
2004-2020
Monash University
2005-2019
Baker Heart and Diabetes Institute
2012-2019
Australian Regenerative Medicine Institute
2018-2019
Royal National Orthopaedic Hospital
2004-2018
Discovery Institute
2018
University of British Columbia
2012-2013
Spinal Cord Injury BC
2013
Highlights•IL-6 trans-signaling recruits macrophages to adipose tissue in HFD-induced obesity•Blocking IL-6 with sgp130Fc prevents ATM accumulation•Prevention of accumulation obesity does not rescue insulin resistance•Blocking exacerbate resistanceSummaryInterleukin-6 (IL-6) plays a paradoxical role inflammation and metabolism. The pro-inflammatory effects are mediated via "trans-signaling," process where the soluble form receptor (sIL-6R) binds activates signaling inflammatory cells that...
Induction of heat shock protein (HSP)72 protects against obesity-induced insulin resistance, but the underlying mechanisms are unknown. Here, we show that HSP72 plays a pivotal role in increasing skeletal muscle mitochondrial number and oxidative metabolism. Mice overexpressing (HSP72Tg) control wild-type (WT) mice were fed either chow or high-fat diet (HFD). Despite similar energy intake when HSP72Tg compared with WT mice, HFD increased body weight, intramuscular lipid accumulation...
A nationwide survey indicates that the American public views electronic computer and its significance in terms of two independent belief-attitude dimensions. The first as an instrument man's purposes-helpful science, industry, space exploration, etc. second portrays machine a relatively autonomous entity can perform functions human thinking. People tend to react with awe sense inferiority this latter conception. Individual variations strength these reactions are related certain personality...
OBJECTIVE The hypothesis that high-fat (HF) feeding causes skeletal muscle extracellular matrix (ECM) remodeling in C57BL/6J mice and this contributes to diet-induced insulin resistance (IR) through the collagen receptor integrin α2β1 was tested. RESEARCH DESIGN AND METHODS association between IR ECM studied fed chow or HF diet. Specific genetic pharmacological murine models were used study effects of on absence IR. role ECM-integrin interaction using hyperinsulinemic-euglycemic clamps...
Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal comprises the vast majority of insulin-sensitive tissue and is a site dysregulation insulin-resistant state. The biochemical histological composition well defined variety species. However, functional consequences adaptations physiological pathophysiological conditions are not understood. regulation complex. Sites involved by three-step process consisting of: (1) delivery muscle, (2)...
AMP-activated protein kinase (AMPK) has been postulated as a super-metabolic regulator, thought to exert numerous effects on skeletal muscle function, metabolism, and enzymatic signaling. Despite these assertions, little is known regarding the direct role(s) of AMPK in vivo, results obtained vitro or situ are conflicting. Using chronically catheterized mouse model (carotid artery jugular vein), we show that regulates metabolism vivo at several levels, with result deficit activity markedly...
The sphingolipids sphingosine-1-phosphate (S1P) and ceramide are important bioactive lipids with many cellular effects. Intracellular accumulation causes insulin resistance, but sphingosine kinase 1 (SphK1) prevents accumulation, in part, by promoting its metabolism into S1P. Despite this, the role of SphK1 regulating action has been largely overlooked. Transgenic (Tg) mice that overexpress were fed a standard chow or high-fat diet (HFD) for 6 weeks before undergoing several metabolic...
Hypothalamic neurons respond to nutritional cues by altering gene expression and neuronal excitability. The mechanisms that control such adaptive processes remain unclear. Here we define populations of POMC in mice are activated or inhibited insulin thereby repress inhibit hepatic glucose production (HGP). proportion was dependent on the regulation receptor signaling phosphatase TCPTP, which is increased fasting, degraded after feeding elevated diet-induced obesity. TCPTP-deficiency enhanced...
We examined the effect of short-term exercise training on skeletal muscle AMP-activated protein kinase (AMPK) signalling and metabolism during prolonged in humans. Eight sedentary males completed 120 min cycling at 66 +/- 1% , then trained for 10 days, before repeating bout same absolute workload. Participants rested 72 h each trial while ingesting a high carbohydrate diet (HCHO). Exercise significantly (P < 0.05) attenuated exercise-induced increases free AMP: ATP ratio glucose disposal...
The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant neuronal NOS, termed nNOS mu. Exercise training increases mu protein levels rat muscle, but data humans are conflicting. We performed two studies to determine 1) whether resting expression greater 10 endurance-trained athletes compared with 11 sedentary individuals (study and 2) intense short-term (10 days) exercise (within whole also within types I, IIa, IIx fibers) eight 2). In study 1, was...
The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with requirements. This coupling is fundamental in the adaptive response to many conditions and impaired disease. We have found that state substantially reduced following exercise, fasting, exposure other stressors C57BL/6 mice. Glucagon receptor signaling was hypothesized mediate this reduction because increased plasma levels of glucagon are characteristic stress hormone stimulates consumption linked...
Hepatic glucagon action increases in response to accelerated metabolic demands and is associated with increased whole body substrate availability, including circulating lipids. The hypothesis that hepatic stimulate AMP-activated protein kinase (AMPK) signaling peroxisome proliferator-activated receptor-α (PPARα) fibroblast growth factor 21 (FGF21) expression a manner modulated by fatty acids was tested vivo. Wild-type (gcgr(+/+)) receptor-null (gcgr(-/-)) littermate mice were studied using...
We compared in human skeletal muscle the effect of absolute vs. relative exercise intensity on AMP-activated protein kinase (AMPK) signaling and substrate metabolism under normoxic hypoxic conditions. Eight untrained males cycled for 30 min conditions (11.5% O(2), 111 +/- 12 W, 72 3% hypoxia Vo(2 peak); 72% Hypoxia) or (20.9% O(2)) matched to same (111 51 1% normoxia 51% Normoxia) (to peak)) (171 18 73 73% Normoxia). Increases (P < 0.05) AMPK activity, AMPKalpha Thr(172) phosphorylation,...
Endothelial nitric oxide synthase (eNOS) is associated with a number of physiological functions involved in the regulation metabolism; however, functional role eNOS poorly understood. We tested hypothesis that critical to muscle cell signaling and fuel usage during exercise vivo, using 16-wk-old catheterized (carotid artery jugular vein) C57BL/6J mice wild-type (WT), partial (+/−), or no expression (−/−) eNOS. Quantitative reductions (∼40%) elicited many phenotypic effects observed enos −/−...
AMP-activated protein kinase (AMPK) has been extensively studied in whole muscle biopsy samples of humans, yet the fiber type-specific expression and/or activation AMPK is unknown. We examined basal and exercise AMPK-alpha Thr(172) phosphorylation subunit (alpha(1), alpha(2), gamma(3)) type I, IIa, IIx fibers human skeletal before after 10 days training. Before training was greatest IIa (P < 0.05 vs. I IIx), while an acute bout increased all 0.05), with increase occurring fibers. Exercise...