A5063814387- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Regulation of Appetite and Obesity
- Protein Tyrosine Phosphatases
- Diabetes and associated disorders
- Galectins and Cancer Biology
- Diet and metabolism studies
- Neuropeptides and Animal Physiology
- Genetics and Neurodevelopmental Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular Disease and Adiposity
- Genetic Syndromes and Imprinting
- Protein Kinase Regulation and GTPase Signaling
- Diet, Metabolism, and Disease
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Diabetes Management and Research
- Lipid metabolism and disorders
- Diabetes Treatment and Management
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- Ubiquitin and proteasome pathways
- Chemotherapy-induced organ toxicity mitigation
- Epigenetics and DNA Methylation
The University of Melbourne
2018-2025
St Vincents Institute of Medical Research
2016-2025
Australian Catholic University
2022-2025
Blacktown & Mount Druitt Hospital
2022
Garvan Institute of Medical Research
2014-2021
St Vincent's Hospital Sydney
2017-2021
Bridge University
2019
UNSW Sydney
2015-2017
St Vincent's Hospital
2015-2016
Monash University
2009-2015
Insulin signaling in the brain has been implicated control of satiety, glucose homeostasis and energy balance. However, insulin is dispensable controlling AgRP or POMC neurons it unclear which other regulate these effects. Here we describe an ancient insulin/NPY neuronal network that governs across phyla.
AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. inhibits fatty acid synthesis and promotes oxidation by phosphorylation acetyl-CoA carboxylase (ACC) 1 at Ser79 ACC2 Ser212. Using mice with Ser79Ala/Ser212Ala knock-in mutations (ACC DKI) we find that inhibition ACC leads to reduced appetite in response fasting or cold exposure. At sub-thermoneutral temperatures, DKI...
Abstract Prader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans. Recent clinical reports have suggested that micro-deletion Snord116 gene cluster can lead to PWS, however, extent contributions encoded snoRNAs unknown. Here we show mice lacking globally low birth weight, increased body weight gain, energy expenditure and hyperphagia. Consistent with this, microarray analysis hypothalamic expression revealed a significant alteration feeding related pathways was also...
Metabolic diseases such as obesity and type 2 diabetes are marked by insulin resistance
Abstract Aims/hypothesis Type 2 diabetes is a chronic metabolic disorder characterised by insulin resistance and sustained hyperglycaemia, major cause of blindness, kidney failure, heart attacks stroke. Our team has recently identified hexosaminidase A (HEXA) as an endocrine factor secreted the liver that regulates sphingolipid metabolism in skeletal muscle. Specifically, HEXA converts GM2 to GM3 gangliosides within cell-surface lipid rafts. Remodelling ganglioside composition enhances IGF1...
Adenosine monophosphate-activated protein kinase (AMPK) regulates multiple signaling pathways involved in glucose and lipid metabolism response to changes hormonal nutrient status. Cell culture studies have shown that AMPK phosphorylation inhibition of the rate-limiting enzyme mevalonate pathway 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase (HMGCR) at serine-871 (Ser871; human HMGCR Ser872) suppresses cholesterol synthesis. In order evaluate role AMPK-HMGCR vivo, we generated...
Abstract Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism Y1R, via non-brain penetrable antagonist BIBO3304, leads significant reduction in body weight gain due enhanced EE thereby reducing fat mass. Specifically thermogenesis brown adipose tissue (BAT) elevated UCP1 accompanied extensive browning white both mice humans....
OBJECTIVE Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/STAT3-signaling pathways in the liver inhibit expression of gluconeogenic genes to decrease hepatic glucose output. The insulin receptor (IR) JAK1 tyrosine kinases STAT3 can serve as direct substrates for T-cell protein phosphatase (TCPTP). Homozygous TCPTP-deficiency results perinatal lethality prohibiting any informative assessment TCPTP's role homeostasis. Here we have used...
Insulin secretion is tightly controlled through coordinated actions of a number systemic and local factors. Peptide YY (PYY) expressed in α-cells the islet, but its role control islet function such as insulin release not clear. In this study, we generated transgenic mouse model (Pyytg/+/Rip-Cre) overexpressing Pyy gene under rat 2 promoter assessed impact islet-released PYY on β-cell function, release, glucose homeostasis mice. Our results show that up-regulation β-cells leads to an increase...
The calcium-calmodulin–dependent protein kinase kinase-2 (CaMKK2) is a key regulator of cellular and whole-body energy metabolism. It known to be activated by increases in intracellular Ca2+, but the mechanisms which it inactivated are less clear. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma, metabolic derangements induced high-fat diet; therefore, elucidating that inactivate has important therapeutic implications. Here we show stimulation cAMP-dependent A...
Dysregulation of cholesterol metabolism in the liver and hematopoietic stem progenitor cells (HSPCs) promotes atherosclerosis development. Previously, it has been shown that HMG-CoA-Reductase (HMGCR), rate-limiting enzyme mevalonate pathway, can be phosphorylated inactivated by metabolic stress sensor AMP-activated protein kinase (AMPK). However, physiological significance AMPK regulation HMGCR to atherogenesis yet elucidated. The aim this study was determine role AMPK/HMGCR axis development...
Single nucleotide polymorphisms in the gene encoding protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with development of autoimmunity. Here we used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice a global deficiency on C57BL/6 background and compared phenotype these Ptpn2−/− (BALB/c-129SJ) generated previously homologous backcrossed onto BALB/c background. exhibited growth retardation median survival 32 days, as 21 days for (BALB/c) mice, but overt signs...
The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake provides an opportunity for new strategies to treat type 2 diabetes insulin resistance, recent genetic pharmacological studies indicating the α2β2γ1 isoform combination as complex primarily responsible. With goal developing α2β2-specific activators, here we perform...
Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of cells (TECs) were pre-treated with (20 µM, 4 h) prior to exposure cisplatin 23 h). increased acetyl-CoA carboxylase phosphorylation,...