A5081488590- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Developmental Biology and Gene Regulation
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Pluripotent Stem Cells Research
- Diet and metabolism studies
- Cancer-related gene regulation
- Congenital heart defects research
- Exercise and Physiological Responses
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Meat and Animal Product Quality
- Sleep and Wakefulness Research
- Cardiovascular Disease and Adiposity
- Neuroscience and Neuropharmacology Research
- Eating Disorders and Behaviors
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Memory and Neural Mechanisms
- Epigenetics and DNA Methylation
Cancer Institute (WIA)
2024
UNSW Sydney
2019-2023
Garvan Institute of Medical Research
2017-2023
St Vincent's Hospital
2018-2023
St Vincent's Clinic
2021-2023
St Vincent's Hospital Sydney
2017-2021
Children's Medical Research Institute
2014-2018
The University of Sydney
2014-2018
SUNY Upstate Medical University
1977
Abstract Aims/hypothesis Pancreatic beta cell dedifferentiation, transdifferentiation into other islet cells and apoptosis have been implicated in failure type 2 diabetes, although the mechanisms are poorly defined. The endoplasmic reticulum stress response factor X-box binding protein 1 (XBP1) is a major regulator of unfolded response. XBP1 expression reduced islets people with but its role adult differentiated unclear. Here, we assessed effects Xbp1 deletion tested whether XBP1-mediated...
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....
Abstract Excess caloric intake results in increased fat accumulation and an increase energy expenditure via diet-induced adaptive thermogenesis; however, the underlying mechanisms controlling these processes are unclear. Here we identify neuropeptide FF receptor-2 (NPFFR2) as a critical regulator of thermogenesis bone homoeostasis. Npffr2 −/− mice exhibit stronger phenotype when fed HFD display exacerbated obesity associated with failure activating brown adipose tissue (BAT) thermogenic...
Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the hypothalamus an important regulator of energy homeostasis; however, specific contributions different CART neuronal populations to this process are not known. Here, we show that depolarization mouse arcuate nucleus (Arc) neurons via DREADD technology decreases expenditure physical activity, while it exerts opposite effects lateral (LHA). Importantly, when stimulating these absence CART, were attenuated. In...
Aguti-related protein (AGRP) neurons in the arcuate nucleus of hypothalamus (ARC), which co-express neuropeptide Y (NPY), are key regulators feeding and energy homeostasis. However, precise role NPY has within these specific pathways that it control still unclear. In this article, we aimed to determine what aspects behaviour homeostasis controlled by originating from AGRP Y-receptor utilised fulfil function. Novel conditional Agrpcre/+;Npylox/lox knockout mice were generated comprehensively...
Rats were fed either a high fat diet (67% of calories as lard) or glucose glucose) for 7-8 days. Basal and insulin stimulated net uptake D (D-L) 2 deoxy by free cells rats depressed. Net transport purified adipocyte plasma membranes red was also diminished. Incubation from with before homogenization membrane preparation increased subsequently in two experiments to greater extent than similar preparations rat rats. These suggest that feeding modifies the so both stimulatory effect on process...
ABSTRACT Lhx1 encodes a LIM homeobox transcription factor that is expressed in the primitive streak, mesoderm and anterior mesendoderm of mouse embryo. Using conditional flox mutation three different Cre deleters, we demonstrated LHX1 required mesendoderm, but not mesoderm, for formation head. enables morphogenetic movement cells accompanies part through regulation Pcdh7 expression. also regulates, genes encoding negative regulators WNT signalling, such as Dkk1, Hesx1, Cer1 Gsc. Embryos...
Failure to secrete sufficient quantities of insulin is a pathological feature type-1 and type-2 diabetes, also reduces the success islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits release in β-cells, show this can be pharmacologically exploited boost secretion. Transplanting islets with deficiency accelerates normalization hyperglycemia chemically induced diabetic recipient mice, which achieved by short-term pharmacological blockade receptors transplanted...
The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and patterning of anterior structures in mouse embryo. knockout embryos fail to form head. Whereas previous studies have shown required visceral endoderm neuroectoderm head formation, its role mesendoderm (AME) has not been assessed specifically. Here, we show tissue-specific ablation AME phenocopies truncation embryonic null mutant. Expression Dkk1 Lhx1, two genes are also disrupted...
Although best known for their involvement in modulating nociception, Neuropeptide FF (NPFF) group peptides have been suggested to fulfil a variety of biological functions such as feeding, anxiety behaviors and thermogenesis. However, evidence supporting these NPFF is mostly pharmacological, leaving the physiological relevance unaddressed. Here we examined impact lack signalling both genders using Npff-/- mouse model. expression restricted spinal cord brainstem while its cognate receptor...
Abstract Peptide YY (PYY), produced by endocrine L cells in the gut, is known for its critical role regulating gastrointestinal functions as well satiety. However, how these processes are integrated with maintaining a healthy gut microbiome composition unknown. Here, we show that lack of PYY mice leads to distinct changes diet‐dependent. While under chow diet only slight differences could be observed, high‐fat (HFD) aggravated differences. Specifically an increased abundance Bacteroidetes...
Peptide YY 3-36 (PYY3-36) is known as a critical satiety factor that reduces food intake both in rodents and humans. Although the anorexic effect of PYY3-36 assumed to be mediated mainly by Y2 receptor, involvement other Y-receptors this process has never been conclusively resolved. Amongst them, Y5 receptor (Y5R) most likely candidate also target for PYY3-36, which considered counteract anorectic effects Y2R activation. In present study, we show short-term treatment diet-induced obese...
Development of the embryonic head is driven by activity gene regulatory networks transcription factors. LHX1 a homeobox factor that plays an essential role in formation head. The loss function results anterior truncation embryo caused disruption morphogenetic movement tissue precursors and dysregulation WNT signaling activity. Profiling expression pattern Lhx1 mutant revealed tissues germ layers acquire posterior characteristics, suggesting required for allocation patterning precursor...
Chronic stress has adverse consequences on many organ systems and physiological processes. However, existing protocols show large variability in response are not suitable for female mice. Here, we provide a step-by-step protocol establishing reliable chronic model mice that can be used variety of settings. This been tested to effective produce consistent several mouse strains (C57BL/6J, 129X1/SvJ, B6.V-Lepob/J) both sexes. For complete details the use execution this protocol, please refer Ip...
Gene expression programs underpin the development of shared phenotypes, yet importance transcript complexity in shaping mammalian evolution remains unclear. Here we present a comprehensive long-read direct RNA sequencing atlas full-length transcripts and their m6A modifications across six tissues (hippocampus, frontal cortex, cerebellum, testes, skeletal muscle, liver) five mammals (human, mouse, rat, dog, cow) non-mammalian out-group (chicken). Our analysis reveals that 29% genes have...