Cardiometabolic Changes After Continuous Positive Airway Pressure Treatment For Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will definitively establish if CPAP can also improve markers of cardio-metabolic health, such as visceral fat, insulin sensitivity, central blood pressure and arterial stiffness. The results of the study will shed light on the broader health consequences of OSA and contributes to the development of more targeted treatment strategies.
Metabolic And Neurobiological Changes After Continuous Positive Airway Pressure Treatment For Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$503,497.00
Summary
CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will definitively establish if CPAP can also improve markers of cardio-metabolic health, such as visceral fat, insulin sensitivity, central blood pressure and arterial stiffness. The results of the study will shed light on the broader health consequences of OSA and contribute to the development of more targeted treatment strategies.
Dietary Fats As Drivers Of Obesity-related Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Obesity leads to diabetes and heart disease but not all body fat seems to be bad. Increased fat around the waist (especially the visceral fat around the intestine and internal organs) is particularly bad. Visceral fat secretes a lot of inflammatory molecules. This research aims to understand how visceral fat becomes inflamed and how we might use diet and other methods to reduce both the amount of visceral fat and its level of inflammation; thus reducing both obesity and its health consequences.
An Examination Of The Contribution Of Visceral Adiposity To Insulin Resistance In Humans.
Funder
National Health and Medical Research Council
Funding Amount
$335,800.00
Summary
The worldwide epidemic of Type 2 diabetes is related to major nutritional and activity changes interacting with a genetic predisposition. The two key defects in Type 2 diabetes are a reduced response to insulin (insulin resistance) and relative failure of insulin production. Insulin resistance is the earliest defect and is closely associated with cardiovascular risk. Obesity generates insulin resistance, but intraabdominal (visceral) fat has particular importance. Visceral fat cells are differen ....The worldwide epidemic of Type 2 diabetes is related to major nutritional and activity changes interacting with a genetic predisposition. The two key defects in Type 2 diabetes are a reduced response to insulin (insulin resistance) and relative failure of insulin production. Insulin resistance is the earliest defect and is closely associated with cardiovascular risk. Obesity generates insulin resistance, but intraabdominal (visceral) fat has particular importance. Visceral fat cells are different to other fat cells; they are very metabolically active and 'spill out' fatty acids indiscriminately contributing to insulin resistance in liver and muscle; they also produce hormones which may modify the action of insulin. We will study people undergoing abdominal surgery. Participants will be (1) normal weight and sensitive to insulin, (2) abdominally overweight and insulin resistant, (3) insulin resistant with Type 2 diabetes. We will document abdominal fat, circulating lipid and hormone levels and insulin action. At surgery fat biopsies will be obtained from (a) inside the abdominal cavity, (b) the fat layer under the abdominal skin and (c) fat in the buttock. The activity of a large number of genes in the fat tissue will be assessed in 8 subjects using DNA array (4 each from Groups 1 and 2). Then a small number of genes will be selected on the basis of different activity in visceral fat from buttock fat, and between insulin sensitive and insulin resistant people. The activity of these genes will be determined in all subjects in the 3 groups. We anticipate identifying a few (perhaps 3) genes whose activity is closely associated with insulin resistance and will examine their capability to block insulin action in a series of animal and cellular studies. These studies should identify specific mechanisms by which visceral fat creates insulin resistance. This would be an important step towards prevention and improved medication for Type 2 diabetes.Read moreRead less
Visceral Sensation In Complicated And Uncomplicated Upper Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$66,929.00
Summary
50% of patients with complications of peptic ulcer (bleeding) and gastroesophageal reflux disease (Barrett's Oesophagus) have no symptoms of their diseases. In contrast, 50% of patients who seek treatment for gastrointestinal symptoms are found to have no cause after investigations. The aims of this study are to explore differences in sensation, muscular function and genetic factors between patients with functional gastrointestinal disorders and patients with complicated organic disorders.
Peroxisome Proliferator-activated Receptors: A Role In The Promotion Of Mammary Gland Carcinogenesis By Dietary Fat.
Funder
National Health and Medical Research Council
Funding Amount
$188,702.00
Summary
Breast cancer is a leading cause of death in Australian women. While some women have a hereditary predisposition to breast cancer, for most women a variety of factors are responsible for their disease. One thing that appears to be important as a cause of breast cancer is our diet. There are many components of the diet that may play a role. One important factor is the amount and type of fat that we consume. Just how dietary fat causes an increase in breast cancer is not known. What this project a ....Breast cancer is a leading cause of death in Australian women. While some women have a hereditary predisposition to breast cancer, for most women a variety of factors are responsible for their disease. One thing that appears to be important as a cause of breast cancer is our diet. There are many components of the diet that may play a role. One important factor is the amount and type of fat that we consume. Just how dietary fat causes an increase in breast cancer is not known. What this project aims to achieve is an understanding of how dietary fat and breast cancer are related. If we can understand this then we can rationally design treatments or a preventative strategy.Read moreRead less
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less