How Subcutaneous Fat Protects the Female Brain

Women’s tendency to store more fat in places like the hips, buttocks and the backs of their arms, called subcutaneous fat, protects against brain inflammation, which can lead to problems like dementia and stroke, at least until menopause, research has found.

Different Fat Patterns Between Men and Women: The Main Reason for Protection Against Inflammation

Men of virtually any age have a greater propensity to accumulate fat around the abdominal area, known as visceral obesity, which is known to be far more inflammatory. And before women reach menopause, men are considered to be at much higher risk for conditions ranging from heart attack to stroke. When people think of protecting women, the first thing that comes to mind is estrogen, which has protective effects. Hormones don’t always play a role, however, according to Alexis M. Stranahan, PhD, a neuroscientist in the Department of Neuroscience and Regenerative Medicine at Augusta University Medical College of Georgia. Diet and genetics are other likely factors that explain the differences commonly attributed to estrogen.

To learn more about how the brain becomes inflamed, the researchers examined the increase in the amount and location of adipose tissue, sex hormone levels and brain inflammation in male and female mice at different time intervals as they became fatter on a high-fat diet. Because obese female mice, like humans, tend to accumulate more subcutaneous fat and less visceral fat than male mice, the researchers argued that the distinctive fat patterns may be a key reason for the protection against inflammation enjoyed by premenopausal females.

Subcutaneous Fat Breakdown Increases Brain Inflammation in Females

They again found the characteristic patterns of fat distribution in males and females in response to a high-fat diet. They found no signs of brain inflammation or insulin resistance, which can also increase inflammation and lead to diabetes, until the female mice reached menopause. At around 48 weeks menstruation stops and the position of fat in the females begins to shift somewhat. They then compared the effects of the high-fat diet, which is known to increase inflammation throughout the body, in mice of either sex after undergoing liposuction-like surgery to remove subcutaneous fat. Subcutaneous fat reduction increased encephalitis in the females without altering estrogen levels and other sex hormones.

Conclusion: The females’ encephalitis looked much more similar to that of the males, including increased levels of classic inflammatory promoters such as the signaling proteins IL-1β and TNF alpha in the brain. When the researchers took subcutaneous fat out of the equation, women’s brains suddenly showed inflammation, as men’s brains do, and they gained more visceral fat. The transition occurred over about three months, which equates to several years in human time.

Only After Menopause Comparable Brain Inflammation As in Males

In comparison, the females who did not have subcutaneous fat removed but ate a high-fat diet showed similar degrees of brain inflammation as the males only after menopause. When mice on a low-fat diet had subcutaneous fat removed at an early age, they developed slightly more visceral fat and slightly more inflammation in the fat. But Stranahan and her colleagues saw no signs of inflammation in the brain.

One lesson to take away from work, according to the experts, is not to have liposuction and to follow a high-fat diet afterwards. Another: BMI, which is simply weight divided by height and is widely used to indicate overweight, obesity, and consequent increased risk of a variety of diseases, is probably not a very meaningful tool. Another simple and more accurate indicator of both metabolic risk and potential brain health is the waist-to-hip ratio, which is also easy to calculate. The key to obesity is where the fat is located.

The Effects of Obesity on The Brain

The new study specifically targets the hippocampus and hypothalamus of the brain. The hypothalamus controls metabolism and exhibits changes in inflammation from obesity that help control conditions that develop as a result throughout the body. The hippocampus, a center of learning and memory, is regulated by but does not control signals associated with these pathologies. While these are good places to start such explorations, other regions of the brain could respond very differently, so she’s already looking at the effects of subcutaneous fat loss in others. With the evidence suggesting that estrogen may not explain the protection women have, Stranahan would like to better define which is the case. One of their suspects is the marked chromosomal differences between males and females.

Stranahan has studied the effects of obesity on the brain for several years and is among the first scientists to show that visceral fat promotes encephalitis in overweight male mice and conversely, subcutaneous fat transplantation reduces their encephalitis. Women also naturally have higher amounts of proteins that can suppress inflammation. Microglia, immune cells in the brain, have been shown to be activated by a high-fat diet in men, but not in women. She notes that some believe that women have higher stores of subcutaneous fat to allow for adequate energy stores for reproduction.