Polycystic ovary syndrome (PCOS) affects a striking 9-21% of women of reproductive age. PCOS is an important health problem and can affect menstrual cycles, fertility and increase risk of diabetes and mood disorders. There is a lack of longitudinal studies that women with PCOS over time to examine the key determinants of PCOS, long-term impact of obesity and factors contributing to PCOS complications.
Polycystic Ovary Syndrome - Targeting The Sympathetic Nervous System To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of ....Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of pharmacological treatment targeting this system.Read moreRead less
NR4A Orphan Nuclear Receptor Signalling In Skeletal Muscle: Evidence For Crosstalk With The Beta-adrenergic Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$323,749.00
Summary
The NR4A subgroup of are 'orphan' members of the nuclear hormone receptor (NR) superfamily (that are all implicated in human disease). NRs are hormone-dependent DNA binding proteins that translate nutritional and pathophysiological signals into gene regulation. The importance of this 'drugable' gene family in the context of promoting and maintaining human health is underscored by the diversity of medicinals associated with dysfunctional hormone signalling, in the context of inflammation, diabete ....The NR4A subgroup of are 'orphan' members of the nuclear hormone receptor (NR) superfamily (that are all implicated in human disease). NRs are hormone-dependent DNA binding proteins that translate nutritional and pathophysiological signals into gene regulation. The importance of this 'drugable' gene family in the context of promoting and maintaining human health is underscored by the diversity of medicinals associated with dysfunctional hormone signalling, in the context of inflammation, diabetes, dyslipidemia, and endocrine disorders (e.g ~15% of the top selling therapeutic compounds target NRs). The NR4A subgroup are stress response genes which are induced by a wide range of physiological stimuli and have been implicated in the response to energy excess (over-eating) and diet induced obesity. The NR4A subgroup are expressed in skeletal muscle, a major mass peripheral tissue that accounts for ~40% of the body mass and energy expenditure. This lean tissue is a major site of fat oxidation, insulin-stimulated glucose utilization and cholesterol metabolism. Therefore this tissue plays a notable role in insulin sensitivity, the blood lipid profile, and energy balance. Accordingly, muscle has a significant role in the progression of dyslipidemia, diabetes and obesity. Surprisingly, the function of the NR4A subgroup in skeletal muscle metabolism has not been examined. Nevertheless, given the data on NR4A mediated gene regulation, and the potential therapeutic utility for the treatment of metabolic disease, the contribution of skeletal muscle to NR4A action must be defined. Correspondingly, the objective of this proposal is to examine the role of the NR4A subgroup and is relevant to understanding the basis of dyslipidemia and obesity.Read moreRead less
Endocrine signalling from bone cells in the regulation of glucose and energy homeostasis. Osteoporosis, obesity and diabetes are increasingly common, all of which are in urgent need of more effective therapies. This project examines powerful neuropeptide signalling pathways that integrate bone homeostasis with whole body energy and glucose balance. Initial studies have defined the efferent hypothalamic pathways of this system and this project will build upon these findings to examine the feedbac ....Endocrine signalling from bone cells in the regulation of glucose and energy homeostasis. Osteoporosis, obesity and diabetes are increasingly common, all of which are in urgent need of more effective therapies. This project examines powerful neuropeptide signalling pathways that integrate bone homeostasis with whole body energy and glucose balance. Initial studies have defined the efferent hypothalamic pathways of this system and this project will build upon these findings to examine the feedback signals produced by bone cells to regulate adipose and pancreatic function. Exploring this entirely new paradigm of skeletal biology, will reveal novel circulating factors capable of regulating adipose and glucose economies, as well as bone mass, thereby offering potential therapies for these debilitating conditions.Read moreRead less
Nuclear Receptor 4A3 Signalling In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$475,745.00
Summary
Nuclear receptors regulate hormonal control of reproduction, endocrine physiology, and metabolism, and are very important in human health. NR4A3 function in peripheral tissues remains illusive. However, it is expressed in skeletal muscle, a tissue that (i) modulates blood lipids, insulin sensitivity and energy balance, and (ii) has an imortant role in diabetes and obesity. Understanding NR4A3 function in metabolism provides a potential platform for therapeutic intervention.
Targeting Nicotinamide Adenine Dinucleotide Biosynthesis To Improve Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Nicotinamide adenine dinucleotide (NAD) is a cellular metabolite that regulates many biological processes. NAD levels decline with age and also in obesity and interventions that increase NAD levels produce favourable metabolic effects. In this proposal we will utilise a range of novel experimental models to define the molecular pathways that mediate the beneficial effects of NAD.