The brain exerts a restraining influence over the heartbeat via the vagus nerves. This is known as cardiac vagal ‘tone’. It is strong when we are healthy but weak when we are sick. It has a positive influence on the health of the heart and perhaps the body generally. Vagal tone comes from the brain but, despite over 150 years’ research, nobody knows exactly where. Using a novel technique, we can track down its origins. This important basic knowledge may lead to ways to improve health.
The Role Of Gastric Vagal Afferents In The Food Intake Reducing Effect Of Oestradiol
Funder
National Health and Medical Research Council
Funding Amount
$317,739.00
Summary
Regulation of food intake is paramount for maintaining health. Nerves from the stomach serve as important regulators of food intake. These nerves can be modulated by chemical substances; however the importance of this modulation is not well defined. The sex steroid, oestradiol, has potent food intake reducing effects, but the mechanism for this is poorly understood. Thus, this fellowship will examine the role that oestradiol has in regulating food intake by acting on nerves within the stomach.
Mechanisms Underlying The Efficacy Of Bariatric Surgery – Insights From Rat Models Of Sleeve Gastrectomy And The Adjustable Gastric Band
Funder
National Health and Medical Research Council
Funding Amount
$868,472.00
Summary
Bariatric surgery is the only effective treatment for morbid obesity. In order to better understand the mechanistic bases of two such procedures, the adjustable gastric band and sleeve gastrectomy, we have developed rodent models. Here we use these models to better understand the physiology and pathophysiology of these surgeries and extend these findings to inform part of a RCT aimed at identifying the basis for effective joint surgical and medicinal treatments of obesity.
Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients r ....Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients reaching the gut cause the release of hormones from cells in the lining of the stomach and intestine. These hormones tell the brain when enough food has been consumed. It used to be thought that the hormones travelled in the blood stream to affect the brain directly. Recently, it has become clear that much of their effect is actually carried by sensory neurons with endings in the lining of the gut. The hormones have a powerful effect the sensory nerve fibres which then send electrical signals in nerve fibres running in the vagus nerve to the brain. Here they make connections which eventually influence the centres that control feeding. There is much to understand about how hormones affect the sensory nerve endings in the wall of the gut, whether all nerve fibres are affected the same way and what sort of information is conveyed to the brain. This project will use electrophysiological methods to identify which nerve fibres are activated by hormones, whether different hormones affect different nerve fibres, which nutrients activate particular nerve fibres and whether nerve fibres make selective contacts with particular hormone-releasing cells. These questions are important for understanding how we normally stop feeding and how drugs might be designed to cause feelings of fullness earlier in each meal.Read moreRead less
Vagal Nerve Stimulation As A Novel Therapy In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,502.00
Summary
Inflammatory bowel disease (IBD) is common exerting a large personal and societal burden to the Australian population. Current medications used to treat IBD are expensive, have many side effects and at times require hospitalisation for their administration. We aim to develop the non invasive and inexpensive technique of vagal nerve stimulation as a novel treatment strategy for IBD.
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Circadian Control Of Peripheral Gastric Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$701,010.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of o ....When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of obesity.Read moreRead less
Interactions Of Gastric Hormones With Vagal Afferent Pathways And The Role Of This System In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$550,918.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and this project aims to find out how to correct this problem in this modern day epidemic.
Mechanosensitive Afferent Nerves And Gastrointestinal Motility
Funder
National Health and Medical Research Council
Funding Amount
$384,693.00
Summary
This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory ne ....This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory nerves there are and whether they all respond to stretch in the same way. We cannot identify their specialised endings in the wall of the gut. While these sensory nerves definitely respond to stretch, they are also known to respond to contractions of the gut wall. Despite this, we do not understand how the normal movements of the gut wall activate them, nor why some movements can lead to pain. Most of the experiments will be carried out on small pieces of tissue taken from humanely killed guinea pigs and studied, under highly controlled conditions, in organ baths. The remainder of the study will be on specimens of human gut tissue obtained at surgery. This project will use new techniques to record sensory nerves during both stretch and contraction of the gut wall to understand what activates them. In addition, their endings will be labelled with dye to reveal their different shapes. Using computerised imaging techniques we will identify whether they respond to particular patterns of movement in the gut wall. Lastly we will record from these sensory neurones in live specimens of human colon to see whether the same types of sensory nerves are present in humans as in the small animals. This study will provide the first comprehensive account of sensory nerves to the gut wall that respond to distension, including those that activate pain pathways. This is a pre-requisite for designing new drugs that will target these nerve cells with minimal side effects.Read moreRead less