At least until menopause, the female inclination to deposit more subcutaneous fat in areas such as the hips, buttocks, and backs of the arms is protective against brain inflammation, which can lead to diseases such as dementia and stroke.
Visceral adiposity, which is known to be significantly more inflammatory, is more prevalent in men of all ages and is referred to as “visceral fat deposition.” And, before women reach menopause, males are regarded as being at a significantly higher risk for inflammation-related conditions, such as heart attack and stroke.
Alexis M. Stranahan, PhD, a neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University, explains, “When people think of protection in women, the first thing that comes to mind is estrogen.” “However, we must move beyond the nave notion that all sex differences are caused by hormone variances and hormone exposure. To be able to treat sex differences and recognize the role that sex plays in differing clinical outcomes, we need a far deeper understanding of the mechanisms underlying sex differences,
Stranahan, corresponding author of a study published in Diabetes, the journal of the American Diabetes Association, explains that diet and heredity are other likely contributors to the variations attributed to estrogen.
She concedes that the discoveries may be heretical and revolutionary and that they even surprised her. “We conducted these tests to determine, first and foremost, whether hormone perturbation, inflammation, or brain alterations occur first.”
To understand more about how the brain becomes inflamed, male and female mice on a high-fat diet were observed over time for changes in the amount and location of adipose tissue, as well as levels of sex hormones and brain inflammation.
Since, similar to humans, obese female mice tend to have more subcutaneous fat and less visceral fat than male mice, the researchers reasoned that the unique fat patterns may be a crucial factor in the protection against inflammation that females experience before menopause.
Males and females exhibited varied patterns of fat distribution in response to a high-fat meal. They did not observe any signs of brain inflammation or insulin resistance, both of which increase inflammation and potentially contribute to diabetes, until the female mice had reached menopause. Menstruation stops around 48 weeks, and female fat distribution begins to resemble that of males.
The researchers next evaluated the effects of the high-fat diet, which is known to raise inflammation throughout the body, on mice of both sexes after liposuction-like surgery to remove subcutaneous fat. They did not remove the ovaries or otherwise directly interfere with normal estrogen levels.
The decrease of subcutaneous fat enhanced brain inflammation in females without altering their estrogen or other sex hormone levels.
Stranahan and her colleagues found that the brain inflammation of females resembled that of males significantly more, with elevated levels of typical inflammation promoters such as the signaling proteins IL-1 and TNF alpha.
“When we removed subcutaneous fat from the equation, the brains of females began to demonstrate inflammation similar to that of males, and females accumulated more visceral fat,” Stranahan explains. Everything was shifted toward the other storage place. The change lasted approximately three months, which is equivalent to several human years.
Stranahan states that only after menopause did females who did not have subcutaneous fat removed but ate a high-fat diet exhibit brain inflammation levels comparable to those of males.
When subcutaneous fat was removed from young mice on a low-fat diet, they developed slightly more visceral fat and a slight increase in fat inflammation. However, Stranahan and her colleagues found no indication of brain inflammation.
Stranahan advises that those who undergo liposuction and then consume a high-fat diet are wasting their time. She adds that BMI, which is calculated by dividing weight by height and is often used to signify overweight, obesity, and consequently a higher risk of a variety of diseases, is likely not a really useful tool. She adds that the waist-to-hip ratio is an easy-to-calculate, more accurate indication of both metabolic risk and possibly brain health.
“We cannot simply state obesity.” We must begin discussing where the fat is. “This is the crucial aspect at hand,” Stranahan argues.
She explains that the current study focused on the hippocampus and hypothalamus regions of the brain. The hypothalamus regulates metabolism and demonstrates alterations in response to inflammation caused by obesity, which aid in the regulation of systemic illnesses that occur as a result. Stranahan emphasizes that the hippocampus, which is a center for learning and memory, is affected by signals associated with these disorders but does not control them. Other parts of the brain may behave quite differently; therefore, she is now examining the effect of subcutaneous fat reduction in other individuals. Stranahan also wishes to clarify the source of females’ protection, as her research suggests estrogen may not be responsible. One of her suspects is the obvious genetic distinction between the XX female and the XY male.
Stranahan has spent years researching the effects of obesity on the brain, and he is among the first scientists to demonstrate that visceral fat promotes brain inflammation in obese male mice, whereas subcutaneous fat transplantation lowers this inflammation. Additionally, females have naturally larger quantities of anti-inflammatory proteins. It has been found that a high-fat diet activates microglia, or brain immune cells, in males but not in females.
She writes that some believe that the reason females have greater subcutaneous fat storage is to provide sufficient energy reserves for reproduction, and she does not dispute the association. Stranahan says there are still many unanswered concerns, such as how much fat is required to sustain fertility versus the amount that may damage your metabolism.
The National Institutes of Health funded the research.
