Energostatic hypothesis
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Amanda Jayne Swan 17:26, 24 October 2011 (UTC) Amanda Jayne Swan 17:27, 24 October 2011 (UTC)
The energostatic hypothesis is based on the idea that, because the brain controls eating, it seems reasonable that hunger might be triggered by a decrease in the availability of energy for the brain itself.[1]
Plan For Article
Introduction How Booth originally came up with the idea for the energostatic hypothesis and his original research methods. Include a timeline diagram here to illustrate the research progress and highlight key areas of progress or new ideas that have changed the original hypothesis. This can also be used to demonstrate current research being undertaken and any significant findings.
The energostatic hypothesis considers how the availability of energy, the product of fuel metabolism, controls feeding behaviour. It had been accepted since the mid 1900's that glucose could mediate hunger levels, this was proposed to be through hepatic glucosensors in the liver that signalled directly to brain through the vagus nerve. It wasn't until Booth (1972) demonstrated that metabolites other than glucose also produced this effect that researchers began to question how this phenomenom came about. This is what initiated the belief that, through a common pathway, recent metabolism of fuels could control subsequent satiety levels and, ultimately, food intake. In this article we will discuss significant research findings that have shaped the hypothesis, the metabolic pathway linking the different fuels and the controversy surrounding the sensing of these metabolic signals. Importantly we will link these mechanisms to possible therapeutic targets in the management of obesity and indicate further research that needs undertaken before the significance of this hypothesis can be fully understood.
The dynamic between Glucose and Lipid systemsEach will have its own sub-section to explain their different mechanisms in triggering the hypothesis and finally how they both combine together to produce the overall effect. A diagram could be used here to illustrate the mechanism of the role of AMPK and how it works.
The role of AMPK In recent years a major development has occurred around the discovery of a protein kinase that is involved in the regulation of energy maintenance. Discovered in 1973 the AMP-activated protein kinase (AMPK) has been found to regulate several key enzymes involved in fatty acid synthesis and steroid production. It is triggered by a decrease in the availability of ATP thereby increasing the AMP:ATP ratio. AMPK is activated to turn off certain ATP pathways that use up reserves in order to conserve energy and allows increased production of ATP in other systems, for example, the oxidation of fatty acids. It is a complex process with many factors regulating its production (As displayed in figure 1-draw diagram to show its production). The initial thought was that it was released as a result of a stressor ie, the lack of ATP. This process occurs at a cellular level but it seems there is now a more central role of AMPK involving the hypothalamic region and regulating appetite. There seems to be a correlation between AMPK and the hormones leptin and ghrelin which have opposite effects on energy uptake. While it is already known that these hormones present a decrease and increase in food uptake respectively it was also shown that AMPK is central to this process.
A study by Andersson et al (2004) injected concentrations of leptin and ghrelin into rats and observed the effects of AMPK In the hypothalamus. It was found that AMPK was decreased within the hypothalamus when leptin was injected while ghrelin caused a subsequent increase in production. The effects were observed approximately one hour of initial exposure to hormones and results were further quantified by measuring production of a downstream product of AMPK, ACC which showed similar significant effects as AMPK. The kinase was then further examined by altering its own production on energy uptake. A mimic of ATP, called ZMP, was synthesised and inserted into the PVN of the hypothalamus (a well-known site of energy uptake and expenditure) and into the third cerebral ventricle. As ZMP could mimic ATP it was able to stimulate production of AMPK. Results showed that it was indeed stimulated and food uptake was increased over an eight hour monitoring period showing that in itself AMPK can have a direct influence over energy intake as well as showing a connection to other satiety hormones.
Though it is now known the role that AMPK plays following activation of leptin or ghrelin it is still an unclear mechanism as to what mechanisms are involved in this.
Where is this mechanism triggered? A lot of research has been conducted into the important of hepatic regulation into energy metabolism. Is this the main sensing organ or are higher centres more crucial in this process.
Short/Long term benefitsWe know that the energostatic hypothesis allows satiety for a period of time but are there any long-term benefits to this mechanism.
Current or Future Directions The theory that AMPK could be used as a potential drug target for combatting obesity. The importance of the Leptin and Ghrelin in changing the perrceptions of the hypothesis. Is it still a relevant theory?
References
- ↑ Booth DA (1972) Postabsorptively induced suppression of appetite and the energostatic control of feeding Physiol Behav 9:199–202 PMID 4654732