Posts tagged lipids
Articles and news from the latest research reports.
Lipid Deficiency Linked to Neuron Degeneration
A type of lipid that naturally declines in the aging brain impacts – within laboratory models used to study Parkinson’s disease – a protein associated with the disease, according to a study co-authored by University of Alabama researchers.
The study, which published today in the Proceedings of the National Academy of Sciences, focuses on lipids, fat-like molecules that naturally occur in organisms, and their potential roles in a complex process that leads to the death of neurons that produce dopamine. When dopamine-producing neurons malfunction or die, this leads to the symptoms associated with Parkinson’s disease.
“This gets right to the heart of understanding, possibly, the mechanism by which one form of lipid is impacting the process of neuron degeneration,” said Dr. Guy Caldwell, UA professor of biological sciences and one of the study’s co-authors.
The study, led by researchers at the Louisiana State University Health Sciences Center, focused on phosphatidylethanolamine, a lipid known as PE. Today’s scholarly article details how low levels of PE lead to high-levels of alpha-synuclein, a protein previously linked to Parkinson’s. It also show the promise a second lipid, ethanolamine, or ETA, has in boosting PE levels.
To function correctly, proteins must fold properly within cells. One misfolding, as can occur when extra copies of the protein alpha-synuclein are present, can lead to others and, subsequently, to aggregation, or clumping, of proteins. Aggregation of proteins can lead to neuron malfunction or cell death.
Previous research had shown that excess alpha-synuclein can serve as an intra-cellular “roadblock,” preventing proteins, dopamine and other things cells need from being delivered to their necessary locations. This delivery disruption can lead to serious disorders.
“That situation is being applied here, but in a different way,” Caldwell said. “We’re gaining a better understanding of the importance these lipids, which are components of cellular membranes, have in maintaining proper trafficking.”
A proper link with alpha-synuclein helps “lipid rafts” in their transport of proteins.
“As the name implies, lipid rafts are like rafts of fat,” Caldwell said. “If alpha-synuclein can’t associate with those rafts, it could be a toxic situation for these cells.”
Using yeast and the tiny nematode C. elegans as laboratory models, the researchers showed they could reverse the delivery problem by adding ETA to the mix.
“This supplementation of ETA basically tells us that if we can restore the amount of PE that is being made, we can create a healthier situation in neurons, and this might help them to survive longer.”
UA’s lead author on the study is Siyuan “Alice” Zhang, a third-year UA doctoral student who works in the Caldwell lab. Dr. Kim Caldwell, UA professor of biological sciences, is also a co-author. LSU’s senior researcher on the project is Dr. Stephan Witt.
Additional study is needed in rodents and patient-derived stem cells before knowing how beneficial the discovery could eventually prove, Caldwell said.
Perhaps one day, Caldwell said, a supplement could be developed to prevent the decline of PE or possibly a drug could be developed to activate an enzyme that converts ETA to PE.
“I think it has promise as a new way of looking at alleviating toxicity,” Caldwell said. “It’s a different angle.”
(Source: uanews.ua.edu)
(Image caption: Membranes containing monounsaturated (left) and polyunsaturated (right) lipids after adding dynamin and endophilin. In a few seconds membranes rich in polyunsaturated lipids undergo many fissions. Credit: © Mathieu Pinot)
Consuming oils with high polyunsaturated fatty acid content, in particular those containing omega-3s, is beneficial for the health. But the mechanisms underlying this phenomenon are poorly known. Researchers at the Institut de Pharmacologie Moléculaire et Cellulaire (CNRS/Université Nice Sophia Antipolis), the Unité Compartimentation et Dynamique Cellulaires (CNRS/Institut Curie/UPMC), the INSERM and the Université de Poitiers investigated the effect of lipids bearing polyunsaturated chains when they are integrated into cell membranes. Their work shows that the presence of these lipids makes the membranes more malleable and therefore more sensitive to deformation and fission by proteins. These results, published on August 8, 2014 in Science, could help explain the extraordinary efficacy of endocytosis in neuron cells.
Consuming polyunsaturated fatty acids (such as omega-3 fatty acids) is good for the health. The effects range from neuronal differentiation to protection against cerebral ischemia. However the molecular mechanisms underlying these effects are poorly understood, prompting researchers to focus on the role of these fatty acids in cell membrane function.
For a cell to function properly, the membrane must be able to deform and divide into small vesicles. This phenomenon is called endocytosis. Generally, these vesicles allow the cells to encapsulate molecules and transport them. In neurons, these synaptic vesicles will act as a transmission pathway to the synapse for nerve messages. They are formed inside the cell, then they move to its exterior and fuse with its membrane, to transmit the neurotransmitters that they contain. Then they reform in less than a tenth of a second: this is synaptic recycling.
In the work published in Science, the researchers show that cell-or artificial membranes rich in polyunsaturated lipids are much more sensitive to the action of two proteins, dynamin and endophilin, which facilitate membrane deformation and fission.Other measurements in the study and in simulations suggest that these lipids also make the membranes more malleable. By facilitating the deformation and scission necessary for endocytosis, the presence of polyunsaturated lipids could explain rapid synaptic vesicle recycling. The abundance of these lipids in the brain could then represent a major advantage for cognitive function.
This work partially sheds light on the mode of action of omega-3. Considering that the body cannot synthesize them and that they can only be supplied by a suit able diet (rich in oily fish, etc.), it seems important to continue this work to understand the link between the functions performed by these lipids in the neuronal membrane and their health benefits.
(Image caption: A cross-section of mouse brain in the nucleus accumbens, a region of the brain known to be involved in reward and motivation, taken by a fluorescence microscope. Blue corresponds to cell nuclei, and green to fluorescence emitted by a green-fluorescent protein (NdT: the original incorrectly states “green fluorescente protein”) that identifies neurons having received the virus that can genetically abolish the expression of lipoprotein lipase protein. Credit: ©Serge Luquet, CNRS/Université Paris Diderot)
Obesity: are lipids hard drugs for the brain?
Why can we get up for a piece of chocolate, but never because we fancy a carrot? Serge Luquet’s team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) has demonstrated part of the answer: triglycerides, fatty substances from food, may act in our brains directly on the reward circuit, the same circuit that is involved in drug addiction. These results, published on April 15, 2014 in Molecular Psychiatry, show a strong link in mice between fluctuations in triglyceride concentration and brain reward development. Identifying the action of nutritional lipids on motivation and the search for pleasure in dietary intake will help us better understand the causes of some compulsive behaviors and obesity.
Though the act of eating responds to a biological need, it is also an essential cultural and social function in our modern societies. Meals are generally associated with a strong notion of pleasure, a feeling that pushes us towards food. Sometimes this is dangerous: 2.8 million people worldwide die from the consequences of obesity each year. Fundamentally, obesity is caused by imbalance between calories consumed and expended. A sedentary life combined with an abundance of sugary, fatty foods provides fertile ground for this disease.
The body uses sugars and fats as energy sources. The brain only consumes glucose. So why do we find an enzyme that can decompose triglycerides, lipids that come in particular from food, at its core, at the heart of the reward mechanism? A team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) led by Serge Luquet, a CNRS researcher, has tackled this fundamental question.
If they have the choice, normal behavior in mice is to prefer a high-fat diet to simpler foods. To simulate the action of a good meal, researchers have developed an approach that allows small quantities of lipids to be injected directly into the brains of mice. They observed that an infusion of triglycerides in the brain reduces the animal’s motivation to press a lever to obtain a food reward. It also reduces physical activity by half. What is more, an “infused” mouse balances its diet between the two food sources offered (high-fat foods and simpler foods).
To ensure that it is indeed the lipids injected that change the mice’s behavior, these Parisian scientists made sure that the lipids could not be detected by the animal’s brain any longer. They managed to remove the specific enzyme for triglycerides by silencing its coding gene, but only at the heart of the reward mechanism. The animal then shows increased motivation to obtain a reward, and if given the choice, consumes much richer food than average. This work echoes the previous work by their colleagues: reducing this enzyme in the hippocampus causes obesity.
Paradoxically, with obesity, blood (and therefore brain) triglyceride levels are higher than average. So obesity is often associated with overconsumption of sugary, fatty foods. The researchers explain this: with long-lasting high exposure to triglycerides, mice always display lower locomotor activity. By contrast, food rewards are still attractive! The ideal conditions for weight gain are therefore in place. At high triglyceride contents, the brain adapts to obtain its reward, similar to the mechanisms observed when people consume drugs.
This work, financed in particular by CNRS and ANR, indicate for the first time that triglycerides from food may act as hard drugs in the brain, on the reward system, controlling the motivational and pleasureseeking component of food intake.