In a study using mice, scientists discovered that the same protein that controls fat metabolism in the liver resides in the hippocampus — the memory center of the brain — and controls memory and learning.
“We need to better understand how fat is connected to memory and learning so that we can develop an effective approach to protect memory and learning,” said Kalipada Pahan, PhD, the Floyd A. Davis professor of neurology at Rush University Medical Center.
According to researchers at Rush University Medical Center in Chicago, in collaboration with the National Institutes of Health, middle-aged people with high amounts of abdominal fat are 3.6 times more likely to develop memory loss and dementia later in life.
The researchers report that they found a high level of Peroxisome proliferator-activated receptor alpha (PPARalpha), which is known to control fat metabolism in the liver, in the hippocampus of the study’s mice.
“While PPARalpha-deficient mice are poor in learning and memory, injection of PPARalpha to the hippocampus of PPARalpha deficient mice improves learning and memory,” said Pahan.
Since PPARalpha directly controls fat metabolism, people with abdominal fat levels have depleted PPARalpha in the liver and abnormal lipid metabolism, the researchers said. At first, these individuals lose PPARalpha from the liver and then eventually from the whole body, including the brain.
That’s why the researchers say that abdominal fat is an early indication of some kind of dementia later in life.
Using a bone marrow chimera technique, researchers were able to create some mice with normal PPARalpha in the liver and depleted PPARalpha in the brain. These mice were poor in memory and learning. On the other hand, mice that have normal PPARalpha in the brain and depleted PPARalpha in the liver showed normal memory, according to the researchers.
“Our study indicates that people may suffer from memory-related problems only when they lose PPARalpha in the hippocampus,” said Pahan.
The researchers note their study shows that PPARalpha also directly stimulates CREB (cyclic AMP response element-binding protein), which is called the master regulator of memory as it controls different memory-related proteins.
“Further research must be conducted to see how we could potentially maintain normal PPARalpha in the brain in order to be resistant to memory loss,” said Pahan.
The study is published in Cell Reports.
Source: Rush University Medical Center