According to new research, subcutaneous fat, which is more common in women, protects against brain inflammation.
Women’s propensity for subcutaneous fat, which is fat stored under the skin, often in places like their hips, buttocks, and backs of their arms, protects against brain inflammation, at least until death. menopause. That’s according to a new study by scientists at Augusta University’s Medical College of Georgia. This is important because brain inflammation can contribute to serious problems like dementia and stroke.
Men of virtually any age, on the other hand, have a greater propensity to deposit fat around major organs in their abdominal cavities. It’s called visceral fat or visceral adiposity, and it’s known to be much more inflammatory. And, before women reach menopause, men are considered to be at much higher risk for inflammation-related issues, from heart attack to stroke.
“When people think of protection in women, their first thought is estrogen,” says Alexis M. Stranahan, PhD, a neuroscientist in the Department of Neurosciences and Regenerative Medicine at Augusta University’s Medical College of Georgia. “But we need to move beyond the simplistic idea that every sex difference involves hormonal differences and hormone exposure. We really need to think more deeply about the underlying mechanisms of sex differences so that we can address them and recognize the role that gender plays in different clinical outcomes.
Diet and genetics are other factors that may explain the differences commonly attributed to estrogen, says Stranahan, corresponding author of a study recently published in the journal American Diabetes Association. Diabetes.
Watch a video showing where male and female mice gain weight on a high fat diet. Although at some point women may have the same amount of visceral fat as men, there is even less inflammation. Credit: Alexis Stranahan, Medical College of Georgia
Stranahan acknowledges that the findings are potentially heretical and groundbreaking and certainly surprising even to her. “We did these experiments to try to figure out, first of all, what happens first, the hormonal disruption, the inflammation, or the brain changes.”
To learn more about how the brain becomes inflamed, researchers looked at increases in the amount and location of fatty tissue as well as levels of sex hormones and brain inflammation in male and female mice at different time intervals as they grew on a high-fat diet. diet.
Since, just like in humans, obese female mice tend to have more subcutaneous fat and less visceral fat than male mice, they speculated that distinctive fat patterns could be a key reason for the protection against infections enjoyed by females before menopause.
In response to a high-fat diet, researchers again found the distinctive patterns of fat distribution in men and women. They found no indicators of brain inflammation or insulin resistance, which also increase inflammation and can lead to diabetes, until the female mice reached menopause. At around 48 weeks, menstruation stops and the positioning of fat on women begins to change somewhat, to look more like men.
They then compared the impact of the high-fat diet, which is known to increase body-wide inflammation, in mice of both sexes after surgery, similar to liposuction, to remove the underside fat. skin. They didn’t do anything to directly interfere with normal estrogen levels, like removing the ovaries.
Loss of subcutaneous fat increased brain inflammation in women without altering levels of their estrogen and other sex hormones.
Bottom Line: Women’s brain inflammation was much more like men’s, including increased levels of classic inflammation promoters like IL-1β and TNF alpha signaling proteins in the brain, Stranahan and colleagues report.
Dr. Alexis Stranahan. Credit: Michael Holahan, University of Augusta
“When we took subcutaneous fat out of the equation, all of a sudden the female brains started showing inflammation like male brains do, and the females gained more visceral fat,” Stranahan says. “It kind of diverted everything to this other storage location.” The transition took place over approximately three months, which translates to several years in human time.
By comparison, it wasn’t until after menopause that women who didn’t remove subcutaneous fat but did follow a high-fat diet showed similar levels of brain inflammation as men, explains Stranahan.
When subcutaneous fat was removed from mice on a low-fat diet at an early age, they developed slightly more visceral fat and slightly more inflammation in the fat. But Stranahan and his colleagues saw no evidence of inflammation in the brain.
One takeaway from work: Don’t do liposuction and follow a high-fat diet afterward, Stranahan says. Another is: BMI, which simply divides weight by height and is commonly used to indicate overweight, obesity, and therefore increased risk of a myriad of diseases, is probably not a tool. very meaningful, she said. An equally simple and more accurate indicator of metabolic risk and potentially brain health is the waist-to-hip ratio, which is also easy to calculate, she adds.
We cannot just talk about obesity. We need to start talking about where the fat is. That’s the critical element here,” Stranahan says.
She notes that the new study looked specifically at the brain’s hippocampus and hypothalamus. The hypothalamus controls metabolism and exhibits changes with the inflammation of obesity that help control the conditions that develop body-wide as a result. The hippocampus, the center of learning and memory, is regulated by signals associated with these pathologies but does not control them, notes Stranahan. While these are good places to start such explorations, other regions of the brain might react very differently, so she is already studying the impact of subcutaneous fat loss in others. Moreover, since his evidence indicates that estrogen may not explain the protection women enjoy, Stranahan wishes to better define what does. One of its suspects is the clear chromosomal differences between XX female and XY male.
Stranahan has been studying the impact of obesity on the brain for several years and is among the first scientists to show that visceral fat promotes brain inflammation in obese male mice, and that conversely, fat grafting subcutaneous reduces their cerebral inflammation. Females also have naturally higher levels of proteins that can suppress inflammation. In men, but not in women, microglia, the brain’s immune cells, have been shown to be activated by a high-fat diet.
She notes that some consider the reason women have higher subcutaneous fat stores to be to allow for sufficient energy stores for reproduction, and she does not dispute the relationship. But many questions remain, such as how much fat is needed to maintain fertility versus how much will affect your metabolism, Stranahan says.
Reference: “Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Dietary Obese Mice” by Alexis M. Stranahan, De-Huang Guo, Masaki Yamamoto, Caterina M. Hernandez, Hesam Khodadadi , Babak Baban, Wenbo Zhi, Yun Lei, Xinyun Lu, Kehong Ding and Carlos M. Sales, November 11, 2022, Diabetes.
DOI: 10.2337/db22-0192
The research was supported by the National Institutes of Health (NIH).
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