MUSCLE METABOLISM AND LEPTIN IN SLEEP-RELATED RESPIRATORY FAILURE - EFFECT OF TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$165,509.00
Summary
Breathing problems are common during sleep affecting at least 10% of the adult population with major disruptions of sleep patterns and lack of oxygen. These problems range from very heavy snoring to actual repeated obstruction in breathing (obstructive sleep apnea or OSA) through to breathing failure both awake and asleep (hypoventilation syndromes). Sleep-breathing disorders are very common in people with obesity and can be treated with special breathing machines. The study comprises of 2 main ....Breathing problems are common during sleep affecting at least 10% of the adult population with major disruptions of sleep patterns and lack of oxygen. These problems range from very heavy snoring to actual repeated obstruction in breathing (obstructive sleep apnea or OSA) through to breathing failure both awake and asleep (hypoventilation syndromes). Sleep-breathing disorders are very common in people with obesity and can be treated with special breathing machines. The study comprises of 2 main parts. 1. We have found previously a close link between breathing problems during sleep and a certain cluster of health complications in obesity including early diabetes and high blood pressure called the metabolic syndrome. However there is very little information on the how this link develops. We will examine how treatment of sleep apnea, and more severe forms of breathing failure during sleep, changes the following - the circulation of blood in muscle, the amount of fat in the muscle, chemical changes within the muscle and alteration in blood vessel size. All these measurements are related to early risk of diabetes and blood pressure. If treatment of breathing problems during sleep improves muscle metabolism, then we may have new additional treatments for the many people with this metabolic syndrome problem 2. In some recent small studies, we have found that a special chemical messenger called leptin is very high in patients with severe breathing failure during sleep. Leptin is actually a messenger produced by body fat that tells the body how to regulate food intake. Leptin also stimulates breathing in rats. We believe that people with these breathing problems in sleep may have problems in sensing leptin in the brain. We will measure leptin before and after treatment of hypoventilation syndrome to see if the level in the body changes. This research may help us find new leptin-related drug treatments for these breathing disorders.Read moreRead less
Gastrointestinal Signals And Cardiovascular Regulation- Implications For Obesity-related Hypertension.
Funder
National Health and Medical Research Council
Funding Amount
$486,886.00
Summary
Obesity is reaching epidemic proportions, and obesity-related hypertension is the leading cause of serious cardiovascular complications. Hormones released from the gut have been implicated in obesity, but their contribution to hypertension has not been studied. Preliminary studies in our laboratory have shown that these hormones participate in signals related to cardiovascular control by acting locally to relay signals to the brain, and may be more important in obesity than previously thought.
The Role Of Central Neural Pathways In The Determination Of Body Fat Mass
Funder
National Health and Medical Research Council
Funding Amount
$73,361.00
Summary
Obesity and its associated health risks are a developing world problem. Fat is not distributed uniformly in an individual; females have more subcutaneous, and males more abdominal, fat. Abdominal fat is associated with the health risks of obesity. The aims of the current project are to examine the neuronal pathways from the brain to fat and the chemicals involved in order to better understand the way in which fat distribution is determined in the body and develop appropriate therapies.
Does Loss Of Melanocortin Glucose Sensing Contribute To Obesity Induced Diabetes?
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
Diabetes is a failure to properly regulate blood glucose levels. Escalating rates of diabetes are a major health problem. Melanocortin neurons in the brain detect blood sugar levels and usually regulate glucose production and utilization, but in obese animals they do not. We have developed a possible therapeutic, which appears to reverse the glucose insensitivity, and rapidly reduces blood glucose in diabetic mice. This project will determine how melanocortins act to regulate glucose levels
Long-term Effects Of Very Low Energy Diet Versus Conventional Diet On Adiposity, Lean Body Mass, Muscle Strength And Bone Density In Obese Adults, And Mechanisms Promoting Changes
Funder
National Health and Medical Research Council
Funding Amount
$925,990.00
Summary
Very low energy diets (VLEDs) are increasingly used to treat obesity. Of concern is the fact that VLEDs induce adaptive responses that can inhibit loss of – and promote regain of – fatness (particularly belly fat) while decreasing lean body mass, muscle strength and bone density. This project will therefore determine whether VLEDs could have negative effects on body composition that increase the risk of metabolic disease, sarcopenia or osteoporosis, and if so, what are the mechanisms involved.
Effects Of Hypothalamus-specific NPY Y1 And Y5 Receptor Deletion In High Fat Diet-induced Obesity
Funder
National Health and Medical Research Council
Funding Amount
$60,420.00
Summary
Obesity is a rising global epidemic, contributing to severe morbidity and mortality and extreme financial burden on society. It is known that the brain controls energy metabolism via molecules such as neuropeptide Y, which has two key receptors involved in weight gain, Y1 and Y5. This study looks at deleting Y1 and Y5 in the brain of overfed subjects to demonstrate their involvement in metabolic adaptations that prevent weight gain in overfeeding, thus developing effective weight loss therapies ....Obesity is a rising global epidemic, contributing to severe morbidity and mortality and extreme financial burden on society. It is known that the brain controls energy metabolism via molecules such as neuropeptide Y, which has two key receptors involved in weight gain, Y1 and Y5. This study looks at deleting Y1 and Y5 in the brain of overfed subjects to demonstrate their involvement in metabolic adaptations that prevent weight gain in overfeeding, thus developing effective weight loss therapies to treat obesity.Read moreRead less
Interactions Between Neuropeptide FF Receptor And Hypothalamic Neuropeptides In The Regulation Of Energy Homeostasis And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$95,733.00
Summary
Despite the alarming obesity epidemic, there currently exists no effective long-term treatment for obesity. Neuropeptide FF and its receptor NPFF2R have an emerging role in regulating food intake and body fat stores. Results from this study will show whether NPFF2R plays an important role in regulating appetite, metabolic rate, body weight and fat stores, thus help to identify whether NPFF2R-targeted therapeutics would confer significant benefit for the long-term treatment of obesity.
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