Summary: An innovative study reveals that neurons may burn fat, challenging the long -date belief that the brain is based solely on glucose for fuel. The researchers discovered that when glucose is scarce, synaptic activity triggers neurons to break down lipid drops and use the resulting fatty acids for energy.
This process of lipid metabolism is regulated by electrical activity and is essential to maintain brain function, especially under stress. The blockade of this fat burning pathway caused a dramatic fall in body temperature, revealing how crucial it is for survival.
Key facts:
Recording as fuel: synaptic activity allows neurons to decompose the drops of fat for energy, particularly when glucose is scarce. GENETIC CLUE: The DDHD2 gene plays a key role in this process; Mutations in it are linked to neurological disorders. FUNCTIONAL EVIDENCE: Blocking of fat burning in mice -induced lethargy, highlighting the importance of lipid metabolism in the brain.
Source: Weill Cornell University
While glucose, or sugar, is a well -known fuel for the brain, Weill Cornell medicine researchers have shown that electrical activity in synapses, unions between neurons where communication occurs, can lead to the use of drops of lipids or fats as a source of energy.
The study, published on July 1 in the metabolism of nature, challenges “the long dogma data that the brain does not burn fat,” said principal researcher Dr. Timothy A. Ryan, professor of biochemistry and biochemistry in anesthesiology, and the tri-institutional teacher in the department of Weill Cornell Medicine biochemistry.
The main author of the document, Dr. Mikesh Kumar, a postdoctoral associate in biochemistry in Weill Cornell Medicine, who has been studying cell biology of fat drops, suggested that it makes sense that fat can play a role as a source of energy in the brain as it does with other metabolically demanding tissues, such as muscle.
The research team was particularly intrigued by the DDHD2 gene, which encodes a lipase or an enzyme that helps break down fat. DDHD2 mutations are linked to a type of hereditary spastic paraplegia, a neurological condition that causes rigidity and progressive weakness in the legs, in addition to cognitive deficits.
Previous investigations of other researchers have shown that blocking this enzyme in mice causes an accumulation of triglycerides, or drops of fat that store energy, through the brain. “For me, this was evidence that perhaps the reason we affirm that the brain does not burn fat is because we never see fat stores,” said Dr. Ryan.
Research shows that lipids have an important role
The current study explored if the drops of lipids that accumulate in the absence of DDHD2 are used as fuel by the brain, particularly when glucose is not present, said Dr. Ryan.
Dr. Kumar discovered that when a synapse contains a drop of lipids full of triglycerides in mice without DDHD2, neurons can decompose this fat in fatty acids and send it to mitochondria, cell energy factories, so they can produce adenosine triphosphate (ATP), the energy that the cell needs to work.
“The process of being able to use fat is controlled by the electrical activity of neurons, and this finding surprised me,” said Dr. Ryan. “If the neuron is busy, it drives this consumption. If it is at rest, the process is not happening.”
In another study, the researchers inject a small molecule into mice to block the carnitine palmitiltransferase 1 (CPT1) enzyme, which helps transport fatty acids to mitochondria for energy production.
The CPT1 block prevented the brain from using fat drops, which then led Torpor, a state similar to hibernation, in which the body temperature quickly moves and the beat slows down.
“This answer convinced us that there is a continuous need for the brain to use these drops of lipids,” said Dr. Ryan.
Implications for future research
This research can promote additional research on neurodegenerative conditions and the role of lipids in the brain. Glucose fluctuations or low glucose levels can occur with aging or neurological disease, but the lipid fatty acids of lipid drops can help maintain the energy of the brain, said Dr. Kumar.
“We do not know where this investigation will go in terms of neurodegenerative conditions, but some evidence suggests that the accumulation of drops of fat in neurons can occur in Parkinson’s disease,” he said.
Researchers must also better understand the interaction between glucose and lipids in the brain, said Dr. Ryan.
“By learning more about these molecular details, we hope to unlock explanations for neurodegeneration, which would give us opportunities to find ways to protect the brain.”
About this research news in metabolism and neuroscience
Author: Corinne Esposito
Source: Weill Cornell University
Contact: Corinne Esposito – University of Weill Cornell
Image: The image is accredited to Neuroscience News
Original research: open access.
“Triglycerides are an important fuel reserve for the function of synapse in the brain” of Timothy A. Ryan et al. Nature metabolism
Abstract
Triglycerides are an important fuel reserve for synapse function in the brain
The proper fuel of the brain is essential to maintain the cognitive function, but the role of the combustion of fatty acids (FA) in this process has been difficult to achieve.
Here we show that the acute blockade of a specific lipase triglycerides, DDHD2 (a genetic driver of the complex hereditary spastic paraplegia), or the CPT1 mitochondrial lipid transporter leads to a rapid appearance of torpor in adult male mice.
These data indicate that neurons in vivo are probably constantly flowing fas derived from lipid drops (LD) through β oxidation to support neuronal bioenergetics.
We show that in dissociated neurons, the electrical silencing or the blockade of DDHD2 lead to the accumulation of neuronal suds, even in the nerve terminals, and that the FA derived from the axonal Sud enter the mitochondria in a manner dependent on the activity to boost the local production of ATP Mithocondrial.
These data show that nerve terminals can use Sud during electrical activity to provide metabolic support and probably have a fundamental role in supporting the neuronal function in vivo.
