A5066349610- Nuclear Receptors and Signaling
- Adipose Tissue and Metabolism
- Liver physiology and pathology
- Retinoids in leukemia and cellular processes
- Exercise and Physiological Responses
- Liver Disease Diagnosis and Treatment
- Neonatal Respiratory Health Research
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Pharmacological Effects and Assays
- Organic Chemistry Cycloaddition Reactions
- Hormonal Regulation and Hypertension
- Macrophage Migration Inhibitory Factor
- Biotin and Related Studies
- IL-33, ST2, and ILC Pathways
- Synthesis of Tetrazole Derivatives
- Congenital Anomalies and Fetal Surgery
- Testicular diseases and treatments
- Hepatitis B Virus Studies
- Sphingolipid Metabolism and Signaling
- Effects and risks of endocrine disrupting chemicals
- Pluripotent Stem Cells Research
- Cholesterol and Lipid Metabolism
- Inflammasome and immune disorders
- Congenital limb and hand anomalies
QIMR Berghofer Medical Research Institute
2016-2025
The University of Queensland
2006-2018
β1–3-Adrenoreceptor (AR)-deficient mice are unable to regulate energy expenditure and develop diet-induced obesity on a high-fat diet. We determined previously that β2-AR agonist treatment activated expression of the mRNA encoding orphan nuclear receptor, NOR-1, in muscle cells plantaris muscle. Here we show significantly transiently NOR-1 (and other members NR4A subgroup) slow-twitch oxidative soleus fast-twitch glycolytic tibialis anterior The activation induced by β-adrenergic signaling...
Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and APP/PS1 transgenic mouse (Tg) model familial AD. Next, profiled extracellular vesicles (EVs) whether they may play a role protective effects VET intranasal administration EVs, purified from blood sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show...
β-Adrenergic receptor (β-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit hypertrophy. We previously demonstrated that (NR4A1) is involved lipolysis gene associated with regulation of lipid homeostasis. Subsequently it was by another group β-AR cold exposure-induced brown adipocytes adipose tissue, respectively. Moreover, NOR-1 (NR4A3) hyperinduced exposure nur77−/− animal model. These studies underscored importance understanding role...
Nuclear hormone receptors (NR) have been implicated as regulators of lipid and carbohydrate metabolism. The orphan NR4A subgroup has emerged metabolic function. Targeted silencing neuron-derived receptor 1 (Nor-1)/NR4A3 in skeletal muscle cells suggested that this NR was necessary for oxidative metabolism vitro. To investigate the vivo role Nor-1, we developed a mouse model with preferential expression activated Nor-1 muscle. In muscle, resulted marked increase in: 1) myoglobin expression,...
Glucocorticoid resistance is a rare genetic condition characterized by reduced sensitivity to cortisol signaling and subsequent hyperactivation of the hypothalamic-pituitary-adrenal axis.The objective was confirm diagnosis glucocorticoid in patient, determine degree suppression ACTH levels response dexamethasone, underlying abnormality functional consequences mutation.The patient presented on first day life with profound hypoglycemia. Initial were appropriately elevated; however, found have...
Systemic administration of beta-adrenoceptor (beta-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context energy homeostasis, importance beta-AR signaling highlighted by inability beta(1-3)-AR-deficient mice regulate expenditure susceptibility diet induced obesity. However, molecular pathways gene expression changes that initiate maintain these phenotypic modulations are poorly understood. Therefore, aim this study was identify...
The mRNA encoding Nor-1/NR4A3 is rapidly and strikingly induced by β2-adrenergic signaling in glycolytic oxidative skeletal muscle. In muscle cells, Nor-1 expression important for the regulation of metabolism. Transgenic muscle-specific activated resulted acquisition an endurance phenotype, increase type IIA/X fibers, increased numbers mitochondria. current study, we used dual-energy x-ray absorptiometry magnetic resonance imaging analysis to demonstrate decreased adiposity transgenic (Tg)...
The retinoic acid receptor-related orphan receptor (ROR) alpha has been demonstrated to regulate lipid metabolism. We were interested in the RORα1 dependent physiological functions skeletal muscle. This major mass organ accounts for ∼40% of total body and significant levels catabolism, glucose disposal energy expenditure. utilized strategy targeted muscle-specific expression a truncated (dominant negative) RORα1ΔDE transgenic mice investigate signaling this tissue. Expression profiling...
Homozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Rorα (also known as Rora) expression in all tissues, display a lean dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) α action skeletal muscle was involved the regulation of glucose metabolism.We used three-armed genomic approach, including profiling, ingenuity analysis quantitative PCR validation identify...
Activating mutations in the MAPK pathway effectors, NRAS or BRAF, are detected over 70% of melanomas. Accordingly, identification downstream targets constitutive signalling melanoma represents a major goal understanding genesis this disease. We report here regulation members NR4A family nuclear receptors by BRAF-MEK-ERK cascade cells. Expression profiling cells which both NR4A1 and NR4A2 have been down-regulated siRNA revealed alterations genes associated with proliferation, survival...
Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing is implicated in endocrine system development function, cell death, cycle, gene expression cancer. Despite its role these processes, little known about function cellular targets breast To identify novel regulated by PRMT6 cancer cells, we used a combination of small interfering RNA exon-specific microarray profiling vitro coupled to vivo validation normal primary human tumours....
The Rar-related orphan receptor-α (Rorα) is a nuclear receptor that regulates adiposity and potential regulator of energy homeostasis. We have demonstrated the Rorα-deficient staggerer (sg/sg) mice display lean obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite brown adipose tissue serves as mechanism to increase expenditure resist obesity. DEXA MRI analysis significantly decreased total fat mass fat/lean ratio male chow-fed sg/sg relative wt mice. In addition,...
Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling physical activity can ameliorate/prevent diseases associated with poor diet lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives reprogramming, improves endurance, oxidative metabolism. The current manuscript investigates association between exercise,...
Serum ferritin concentrations increase during hepatic inflammation and correlate with the severity of chronic liver disease. Here, we report a molecular mechanism whereby heavy subunit (FTH) contributes to inflammation. We found that FTH induced activation NLRP3 inflammasome secretion proinflammatory cytokine interleukin-1β (IL-1β) in primary rat stellate cells (HSCs) through intercellular adhesion molecule–1 (ICAM-1). FTH–ICAM-1 stimulated expression Il1b , activation, processing IL-1β...
We and others have previously demonstrated that congenital deficiency of the nuclear hormone receptor, Rorα1, in staggerer (sg/sg) mice results resistance to diet-induced obesity increased insulin sensitivity. Paradoxically, sg/sg are susceptible atherosclerosis display impaired innate immunity, underscoring regulatory links between metabolic disease, inflammation, susceptibility infection. Here, we present novel evidence Rorα1 regulates immune function by demonstrating phagocytosis mice....
Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic diseases (i.e., viral hepatitis, non-alcoholic fatty disease, metabolic cancer) requires experimental manipulation animal models in vitro cell cultures. Both techniques have limitations, such as requirement large numbers animals for vivo manipulation. However, cultures do not reproduce structure function multicellular environment. The use precision-cut slices is a technique which uniform...
Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic diseases (i.e., viral hepatitis, non-alcoholic fatty disease, metabolic cancer) requires experimental manipulation animal models in vitro cell cultures. Both techniques have limitations, such as requirement large numbers animals for vivo manipulation. However, cultures do not reproduce structure function multicellular environment. The use precision-cut slices is a technique which uniform...
Abstract Poor maternal diet during pregnancy predisposes to severe lower respiratory tract infections (sLRI) in infancy, which turn, increases childhood asthma risk, however the underlying mechanisms remain poorly understood. Here, we show that offspring of high fat (HFD)-fed mothers (‘HFD-reared pups’) developed a sLRI following pneumovirus inoculation early-life and subsequent later-life upon allergen exposure. Prior infection, HFD-reared pups microbial dysbiosis low-grade systemic...
A poor maternal diet during pregnancy predisposes the infant to severe lower respiratory tract infections (sLRIs), which, in turn, increases childhood asthma risk; however, underlying mechanisms remain poorly understood. Here, we show that offspring of high-fat (HFD)-fed mothers (HFD-reared pups) developed an sLRI following pneumovirus inoculation early life and subsequent later upon allergen exposure. Prior infection, HFD-reared pups microbial dysbiosis low-grade systemic inflammation...