Subcutaneous beige fat protects the brain from dementia

Research by scientists at the Medical College of Georgia at Augusta University has shown that beige fat cells in subcutaneous fat play an important role in reducing white fat-related inflammation and provide the brain with Protection against dementia
.

In the subcutaneous fat of "pear-shaped" people, beige fat cells are usually mixed with white fat cells

This research team led by neuroscientist Dr.

Alexis M.

Visceral fat around organs is mainly composed of white fat cells, which store energy in the form of triglycerides.
Triglycerides are another type of fat found in the blood and are a high risk factor for heart disease and stroke
.

In contrast, especially in young people, subcutaneous fat, or subcutaneous fat tissue (sitting), is a mixture of white and light brown fat cells, these beige cells are more like brown fat cells, they are rich in mitochondria and used effectively Fat and sugar generate heat through thermogenesis

It is said that exercise and cold exposure will cause the so-called "whitening" of white fat cells
.

In adults, brown fat is mainly located between the shoulder blades and the upper chest

Pear-shaped people, whose weight is generally distributed relatively evenly, are considered to reduce the problems of metabolic diseases, such as the risk of heart disease and diabetes, as well as cognitive decline.
Compared with "apple-shaped" people, more personal fat accumulates in them.
In the middle, often in internal organs such as the liver, Stranahan explained
.

Although there are relatively few studies focusing on subcutaneous obesity and cognitive decline, the data does show that the "pear-shaped" distribution of body fat does not increase the incidence of mild cognitive impairment or dementia.

Beige adipocytes interact with immune cells, and "beige" is sitting with anti-inflammatory cytokines that induce IL4
.

In their research, the research team studied the interaction between immunomodulatory beige fat cells and cognition through a series of dietary obesity, in male mice, sitting in transplant experiments

In some of their studies, the scientists used male mice with a specific gene knocked out.
This gene prevents yellowing or browning of subcutaneous fat cells, effectively making subcutaneous fat more like visceral fat
.

It is known that when fed a high-fat diet (HFD), these mice develop diabetes more quickly than those with normal amounts of beige fat

Through their research, the research team showed that within four weeks of eating a high-fat diet, normal mice and knockout mice gained approximately the same amount of weight, while mice without functional beige fat showed signs of gain in the test.
With accelerated cognitive dysfunction, their brains and bodies show a strong, rapid inflammatory response to HFD, including activation of microglia (innate immune cells in the brain), which may further aggravate inflammation, leading to dementia and other brains Problem
.

Therefore, without beige fat cells, subcutaneous fat begins to become more like dangerous visceral fat in the face of a high-fat diet, Stranahan said

 

The research team pointed out: “Mice lacking beige fat cells show stronger pro-inflammatory responses to high-fat diets in the brain and surrounding areas, and are more prone to cognitive deficits and hippocampal synaptic dysfunction
.
” Stranahan last year The report pointed out that visceral obesity sends signals to immune cells in the brain, triggers inflammation, and ultimately impairs cognitive ability
.
"This is a very different signature," she said
.

 

Even before they developed diabetes, the microglia of these 20-something mice had a large number of inflammatory markers
.
Interestingly, normal (wild type; control mice also turned on these markers, but also turned on anti-inflammatory markers, apparently to reduce any response
.
Normally, mice need about three on a high-fat diet.
It takes only one month to show the beige fat knockout response that researchers have observed in one month
.

To further explore the effects of gray-brown fat, the research team transplanted subcutaneous fat from young, thin, healthy mice into the visceral chambers of other normal but now obese mice.
These mice appeared after 10 to 12 weeks of a high-fat diet.
Behavior similar to dementia
.
They found that subcutaneous fat transplantation can improve memory and restore the basically normal synaptic plasticity in the hippocampus—the ability to adapt to connections between neurons so that they can communicate—the hippocampus is the center of learning and memory deep in the brain
.
"Subcutaneous fat transplantation restored hippocampal-dependent memory in Wt recipients who were obese on a diet and induced a unique microglia phenotype characterized by the co-induction of pro-inflammatory and anti-inflammatory markers," the authors wrote
.
These positive changes seem to depend on the beige fat cells in the donor's subcutaneous fat, because the research team found that the transplantation after the removal of beige fat did not have a Improve the cognitive ability of obese mice
.

Fat is rich in immune cells, which can promote and calm inflammation
.
Stranahan’s research team discovered that beige fat continues to interact with these immune cells to induce the anti-inflammatory cytokine IL4 in subcutaneous fat
.
Stranahan pointed out that, conversely, cold also needs IL4 to stimulate fat secretion
.
Researchers have shown that fat also induces IL4 (a key driver of immune response) in microglia and T cells in the meninges.
Meninges is a multi-layered cap covering the brain that helps protect the brain
.
Another experiment found that T cells in the choroidal plexus that produce cerebrospinal fluid have the effect of inhibiting IL-4 induction
.
"Induction of IL4 in the lymphocytes of the meninges and choroid plexus requires beige adipocytes, and recipient-derived lymphocytes for the cognitive effects of SAT transplantation," they commented
.
The results of the study show that IL-4 is directly involved in the communication between beige fat cells and hippocampal neurons
.

"If you've heard this song in the camp, it's a bit like "Whisper Down the Lane" (Whisper Down the Lane)," Stranahan said, which seems to be a calming link of communication
.
"If we can find out that it is beige fat that limits inflammation, maybe it is beige fat that improves brain plasticity, then maybe we can imitate, with drugs or cold-stimulated beige, and even put some of your subcutaneous fat when you are young, freeze, etc.
You will return it to you when you grow up
.
"

When Stranahan and her team studied further, they found that the transplanted beige fat cells called T cells in the recipient's own meninges, rather than immune cells derived from the transplanted fat, that called for active protection
.
There is evidence that in chronic obesity, the body’s own immune cells can reach the brain.
In this case, there is no evidence that the donor’s immune cells are on the journey
.
"There is no indication that donor-derived lymphocytes are traded between fat and the brain, but recipient-derived lymphocytes are necessary for the effect of transplantation on cognition and microglia morphology," the team commented
.

Stranahan said: "This is very exciting, because we have found a way to allow peripheral immune cells to interact with the brain to promote cognitive ability
.
" He pointed out that immune cells can also do a lot in the brain.
Bad things, such as causing stroke and Alzheimer's disease
.

Many of her goals include learning more about the importance of where to place fat grafts, such as whether transferring subcutaneous fat to the subcutaneous area can better prevent cognitive decline; whether transplanting visceral fat under the skin can reduce its damaging effects ; Better understand how subcutaneous fat conveys a seemingly positive anti-inflammatory message
.
She also wants to explore these issues in female mice, because the current research is limited to male mice
.
But she said that Stranahan's team and others have discovered the importance of intrinsic fat distribution, which may be a biomarker for those who are at greatest risk of cognitive decline
.

The obesity stage may be another factor, because she also has early evidence that the longer the high-fat diet is maintained, the more subcutaneous fat increases, and its protective ability decreases, and visceral fat increases
.
Stranahan pointed out that even healthy, non-obese young people, visceral fat can produce higher levels of underlying inflammation
.

Stranahan and colleagues reported in 2015 that a high-fat diet caused microglia to become inactive and begin to eat up the connections between neurons
.
She emphasized that she does not want the latest research results to cause excessive attention to overweight individuals, but believes that this work is more about better identification of risk factors and different intervention points and methods that suit individual needs
.