Posts tagged energy metabolism

Posts tagged energy metabolism
The disrupted metabolism of sugar, fat and calcium is part of the process that causes the death of neurons in Alzheimer’s disease. Researchers from Karolinska Institutet in Sweden have now shown, for the first time, how important parts of the nerve cell that are involved in the cell’s energy metabolism operate in the early stages of the disease. These somewhat surprising results shed new light on how neuronal metabolism relates to the development of the disease.
In the Alzheimer’s disease brain, plaques consisting of so called amyloid-beta-peptide (Aβ) are accumulated. It is also a well-known fact that the nerve cells of patients with Alzheimer’s disease have problems metabolising for example glucose and calcium, and that these disorders are associated with cell death. The metabolism of these substances is the job of the cell mitochondria, which serve as the cell’s power plant and supply the cell with energy.
However, for the mitochondria to do this, they need good contact with another part of the cell called the endoplasmic reticulum (ER). The specialised region of ER that is in contact with mitochondria is called the MAM region. Earlier studies on yeast and other types of cells have shown that the deactivation of certain proteins in the MAM region disrupt the contact points between the mitochondria and the ER, preventing the delivery of energy to the cell and causing cell death.
Now for the first time, researchers at Karolinska Institutet have studied the MAM region in nerve cells, and examined the interaction between the mitochondria and the ER in early stage Alzheimer’s disease. Although at this point in the development of the disease Aβ has not formed large, lumpy plaques, symptoms still appear, implying that Aβ that has not yet formed plaque is toxic to neurons.
The team’s results are slightly surprising. When nerve cells are exposed to low doses of Aβ, it leads to an increase in the number of contact points between the mitochondria and the ER, causing more calcium to be transferred from the ER to the mitochondria. The resulting over-accumulation of calcium is toxic to the mitochondria and affects their ability to supply energy to the nerve cell.
“It’s urgent that we find out what causes neuronal death if we’re to develop molecules that check the disease,” says Maria Ankarcrona, docent and researcher at the Department of Neurobiology, Care Sciences and Society, and the Alzheimer’s Disease Research Centre of Karolinska Institutet. “In the long run we might be able to produce a drug that can arrest the progress of the disease at a stage when the patient is still able to manage their daily lives. If we can extend that period by a number of years, we’d have made great gains. Today there are no drugs that affect the actual disease process.”
The researchers conducted their studies on mice bred to develop symptoms of Alzheimer’s disease. They also studied nerve cells from deceased Alzheimer’s patients and neurons cultivated in the laboratory.
(Source: alphagalileo.org)
Our internal clocks can become ticking time bombs for diabetes and obesity
New research in The FASEB Journal using mice suggests that disrupting our internal clocks can lead to a complete absence of 24-hour bodily rhythms and an immediate gain in body weight
If you’re pulling and all-nighter to finish a term paper, a new parent up all night with a fussy baby, or simply can’t sleep like you once could, then you may be snoozing on good health. That’s because new research published in The FASEB Journal used mice to show that proper sleep patterns are critical for healthy metabolic function, and even mild impairment in our circadian rhythms can lead to serious health consequences, including diabetes and obesity.
"We should acknowledge the unforeseen importance of our 24-hour rhythms for health," said Claudia Coomans, Ph.D., a researcher involved in the work from the Department of Molecular Cell Biology in the Laboratory of Neurophysiology at Leiden University Medical Center in Leiden, Netherlands. "To quote Seneca ‘We should live according to nature (secundum naturam vivere).’"
To make this discovery, Coomans and colleagues exposed mice to constant light, which disturbed their normal internal clock function, and observed a gradual degradation of their bodies’ internal clocks until it reached a level that normally occurs when aging. Eventually the mice lost their 24-hour rhythm in energy metabolism and insulin sensitivity, indicating that relatively mild impairment of clock function had severe metabolic consequences.
"The good news is that some of us can ‘sleep it off’ to avoid obesity and diabetes," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The bad news is that we can all get the metabolic doldrums when our normal day/night cycle is disrupted."
Hypothalamic control of energy balance: insights into the role of synaptic plasticity
The past 20 years witnessed an enormous leap in understanding of the central regulation of whole-body energy metabolism. Genetic tools have enabled identification of the region-specific expression of peripheral metabolic hormone receptors and have identified neuronal circuits that mediate the action of these hormones on behavior and peripheral tissue functions. One of the surprising findings of recent years is the observation that brain circuits involved in metabolism regulation remain plastic through adulthood. In this review, we discuss these findings and focus on the role of neurons and glial cells in the dynamic process of plasticity, which is fundamental to the regulation of physiological and pathological metabolic events.

Circadian rhythms can be modified for potential treatment of disorders
UC Irvine-led studies have revealed the cellular mechanism by which circadian rhythms – also known as the body clock – modify energy metabolism and also have identified novel compounds that control this action. The findings point to potential treatments for disorders triggered by circadian rhythm dysfunction, ranging from insomnia and obesity to diabetes and cancer.
UC Irvine’s Paolo Sassone-Corsi, one of the world’s leading researchers on the genetics of circadian rhythms, led the studies and worked with international groups of scientists. Their results are detailed in two companion pieces appearing this week in the early online edition of the Proceedings of the National Academy of Science (1 , 2).
“Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms,” said Sassone-Corsi, the Donald Bren Professor of Biological Chemistry. “The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Disruption of these rhythms can profoundly influence human health.”
He added that up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms.