Determinants Of Brown Adipose Tissue Activation - Implication For The Regulation Of Energy Balance And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$617,192.00
Summary
One of the most important recent findings in the biology of obesity has been the revelation that brown adipose tissue (BAT) is present and functional in adult humans. Even more important, the amount of BAT seems to be related to the extent of obesity. The challenge now is to harness the means by which BAT is activated. Understanding the central neural control pathways and the rate limiting steps in the BAT itself will pave the way for new anti-obesity strategies.
Beige fat is a recently described kind of fat which instead of storing fat and contributing to obesity burns energy and burns glucose. It helps to combat obesity and diabetes. If it could be increased and switched on, it would help to treat obesity and diabetes. This grant will study a new pathway to try to increase the amount of beige fat and to increase its activity.
We use a mouse model of inflammatory bowel disease (IBD) to determine how sensations from the inflamed gut are processed in the spinal cord. Over 60,000 Australians suffer from IBD and debilitating pain is a major symptom. Surprisingly, we know very little about how pain signals originating in the normal or the diseased gut are organised and processed in the central nervous system. Obtaining such information is a necessary first step before we can develop therapies to relieve gut pain.
Silencing Visceral Nociceptors By Targeting NaV1.1: A Novel Therapeutic Approach For Treating Irritable Bowel Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$696,809.00
Summary
Patients with Irritable Bowel Syndrome suffer from chronic abdominal pain and co-morbidities such as over-active bladder. These symptoms arise from sensory nerve fibres in the colon and bladder that signal pain to innocuous stimuli. We are excited to report that a specific voltage-gated sodium channel, called NaV1.1, plays a key pathological role in generating these symptoms. Here, we will specifically target and block NaV1.1 expressing pain-sensing neurons, provide key advances for therapies.
Is Overactive Bladder A 'Bladder Itch'? Identification Of Itch Specific Pathways Within The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$720,585.00
Summary
Overactive bladder is a leading cause of nocturia, urgency and incontinence. These symptoms arise from sensory nerve fibres in the bladder. We have identified key irritant mechanisms, including the bile acid receptor TGR5 and Mrgpr family, thought to only exist in the skin, also innervate the bladder. We hypothesis that the clinical entity overactive bladder, is triggered by pathological activation of bladder afferents by such irritants and that overactive bladder is essentially a bladder itch.
A Novel Technique For Prolonged Silencing Of Visceral Pain Without Opiates
Funder
National Health and Medical Research Council
Funding Amount
$637,383.00
Summary
There has been substantial interest in the community for pain relief without opiates. This project demonstrates a new strategy to suppress pain at the source for prolonged periods, by suppressing activity in the sensory nerve endings that detect pain, not by acting in central pathways like opiates. To do this, we use a harmless virus to shut down a vital sodium channel for pain perception. These experiments use techniques that were recently developed in our lab and cant be performed elsewhere.
In men, oestrogen may be important for strong bones and maintaining a healthy weight. Men with prostate cancer are given medical castration treatment to decrease testosterone, because testosterone is required for prostate cancer growth. Because oestrogen is derived from testosterone, they also have very low oestrogen levels. We want to conduct a trial in these men to find out whether giving back oestrogen will prevent bone loss and weight gain, among other health benefits.
Identifying Why Some People Consume Excess Dietary Fat. A Twin Study
Funder
National Health and Medical Research Council
Funding Amount
$365,462.00
Summary
Obesity is a significant public health problem, yet some individuals are less susceptible to the development of obesity. High fat eating patterns are commonly associated with overweight/obesity. The taste system is the gatekeeper of digestion and the sense of taste responds to fat, and that the fat taste response is associated with obesity. Using twins as subjects to disentangle the influences of 'nature and nuture', in this project we will identify the mechanisms responsible for linking fat tas ....Obesity is a significant public health problem, yet some individuals are less susceptible to the development of obesity. High fat eating patterns are commonly associated with overweight/obesity. The taste system is the gatekeeper of digestion and the sense of taste responds to fat, and that the fat taste response is associated with obesity. Using twins as subjects to disentangle the influences of 'nature and nuture', in this project we will identify the mechanisms responsible for linking fat taste response to development of obesity.Read moreRead less
An Essential Role For Skeletal Muscle FoxO1 In Protecting Against Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Skeletal muscle is the largest organ in the human body and accounts for approximately 80% of glucose disposal after a meal. We have identified a transcription factor, namely FoxO1, that appears protect against obesity-induced insulin resistance by promoting energy consumption. This project will examine whether skeletal muscle specific activation of FoxO1 is a possible therapeutic target for the treatment of obesity-induced insulin resistance.
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.