Women’s propensity to deposit more fat in places such as the hips, buttocks and the backs of the arms, so-called subcutaneous fat, protects against brain inflammation, which can lead to problems such as dementia and strokes, at least until menopause, scientists report. .
Sex differences in adipose tissue distribution determine susceptibility to neuroinflammation in dietary obesity mice Summary Preferential energy storage in subcutaneous adipose tissue (SAT) confers protection against obesity-induced pathophysiology in women. Females also exhibit different immune responses, relative to males. These differences are often attributed to sex hormones, but the reciprocal interactions between metabolism, immunity, and gonadal steroids remain poorly understood. Here, we systematically characterized adipose tissue hypertrophy, sex steroids, and inflammation in male and female mice after increasing the duration of high-fat diet (HFD)-induced obesity. After observing that sex differences in adipose tissue distribution before DH were correlated with durable protection against inflammation in women, we hypothesized that a priori differences in the proportion of subcutaneous to visceral fat could mediate in this relationship. To test this, male and female mice received SAT lipectomy (LPX) or sham surgery before the HFD challenge, followed by analysis of glial reactivity, adipose tissue inflammation, and reproductive steroids. Because LPX eliminated female resistance to the proinflammatory effects of HFD without changing circulating sex hormones, we conclude that the sexually dimorphic organization of subcutaneous and visceral fat determines susceptibility to inflammation in obesity. |
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Men of virtually any age have a greater propensity to deposit fat around the major organs in their abdominal cavity, called visceral adiposity, which is known to be much more inflammatory. And, before women reach menopause, men are considered to be at much higher risk of inflammation-related problems, from heart attack to stroke.
“When people think about protecting women, their first thought is estrogen,” says Alexis M. Stranahan, PhD, a neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University. “But we need to get beyond the kind of simplistic idea that every sex difference involves hormonal differences and hormonal 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 sex plays in different clinical outcomes."
Diet and genetics are other likely factors explaining the differences widely attributed to estrogen, says Stranahan, corresponding author of a study in the American Diabetes Association’s journal Diabetes.
She acknowledges that the findings are potentially heretical and revolutionary and certainly surprising even to her. "We did these experiments to try to determine, first of all, what happens first, the hormonal disruption, the inflammation or the brain changes."
To learn more about how the brain becomes inflamed, they looked at increases in the amount and location of fatty tissue, as well as sex hormone levels and brain inflammation in male and female mice at different time intervals as they gained weight. a diet rich in fat. Since, like people, obese females tend to have more subcutaneous fat and less visceral fat than males, they reasoned that distinctive fat patterns could be a key reason for the protection against inflammation that females enjoy before the menopause.
They again found distinctive patterns of fat distribution in men and women in response to a high-fat diet. They found no indicators of brain inflammation or insulin resistance, which also increase inflammation and can lead to diabetes, until the females reached menopause. Around 48 weeks, menstruation stops and the position of the fat in women begins to change a little, to be more like that of men.
They then compared the impact of the high-fat diet, which is known to increase inflammation throughout the body, in mice of both sexes after surgery, similar to liposuction, to remove subcutaneous fat. They did nothing to directly interfere with normal estrogen levels, such as removing the ovaries.
Losing subcutaneous fat increased brain inflammation in women without changing levels of estrogen and other sex hormones.
Bottom line: Women’s brain inflammation looked much more like men’s, including elevated levels of classic inflammation promoters like the signaling proteins IL-1β and TNF alpha in the brain, Stranahan and colleagues report. .
"When we took subcutaneous fat out of the equation, suddenly women’s brains started showing inflammation in the same way as men’s brains, and women gained more visceral fat," Stranahan says. "It kind of diverted everything to that other storage location." The transition occurred over about three months, which translates to several years in human time.
By comparison, it was only after menopause that women who did not have subcutaneous fat removed but who ate a high-fat diet showed similar levels of brain inflammation to men, Stranahan says.
When subcutaneous fat was removed from mice on a low-fat diet at a young age, they developed a little more visceral fat and a little more inflammation in the fat. But Stranahan and his colleagues saw no evidence of inflammation in the brain.
A take-home lesson from work: Don’t get liposuction and then go on a high-fat diet, Stranahan says. Another is: BMI, which simply divides weight by height and is commonly used to indicate overweight, obesity and, consequently, a higher risk of a wide variety of diseases, is probably not a very meaningful tool, he says. . An easy and more accurate indicator of both metabolic risk and potential brain health is the waist-to-hip ratio, which is also easy to calculate, she adds.
“We can’t just say obesity. We have to start talking about where the fat is. That’s the critical element here,” Stranahan says.
She notes that the new study specifically looked 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 throughout the body as a result. The hippocampus, a learning and memory center, is regulated by signals associated with these pathologies but does not control them, Stranahan points out. While these are good places to start such explorations, other brain regions could respond very differently, which is why she is already looking at the impact of subcutaneous fat loss on others. Additionally, since her evidence indicates that estrogen may not explain the protection women have, Stranahan wants to better define what does. One of the suspects is the clear chromosomal differences between the XX female and the XY male.
Stranahan has been studying the impact of obesity on the brain for several years and is one of the first scientists to show that visceral fat promotes brain inflammation in obese male mice and, conversely, subcutaneous fat transplantation reduces inflammation cerebral. Women also naturally have higher levels of protein that can reduce inflammation. It has been shown that in men, but not women, microglia, the brain’s immune cells, are activated by a high-fat diet.
She notes that some consider the reason women have larger reserves of subcutaneous fat to enable sufficient energy reserves for reproduction, and she does not question the relationship. But many questions remain, such as how much fat is needed to maintain fertility versus the level that will affect your metabolism, Stranahan says.
The research was supported by the National Institutes of Health.
