Estrogen converts dangerous fat to healthier fat — even in a man.
New research shows that molecules that hold estrogen can help or hinder fat cell growth, which helps them regulate risk of metabolic diseases, Deborah Clegg of the University of Texas Southwestern Medical Center at Dallas reported October 20 at a symposium for science writers.
Women and men tend to carry fat in different parts of their bodies: men in their guts, women in their butts. More generally, women hold fat in a concentrated layer directly under their skin, called subcutaneous fat. Men’s fat tends to lie inside the abdomen near their organs.
This is bad news for men: Belly fat is highly associated with obesity-related diseases. Jumbo fat cells in obese people secrete hormones that go directly into internal organs like the liver and can inflame the organs. Hormones from subcutaneous fat, on the other hand, go into the bloodstream, where they do less harm.
But there’s bad news for women, too. When women hit menopause, their fat relocates to their guts.
Clegg wanted to find out why.
“We wanted to ask a very silly question: Is a male fat cell the same thing as a female fat cell?” Clegg said at the Council for the Advancement of Science Writing meeting in Austin, Texas. “No one had ever asked that question, which seemed bizarre to me.”
One reason for the oversight was that female rats had been largely absent from previous studies, partially because their four-day estrous cycle made research difficult. “Nobody ever does female rodent research,” Clegg said. “Male researchers hate working with female rats.”
Clegg found that male and female rats have the same fat distribution patterns as humans.
Female rats whose ovaries had been removed also redistributed their fat from under their skin into their bellies. But when she gave them estrogen injections every four days, mimicking their previous cycles, rats’ fat stayed in the healthier form.
To zoom in on estrogen’s effects, Clegg engineered male and female rats that lacked the gene for a molecule called estrogen receptor alpha that grabs on to estrogen. Her earlier studies of human fat cells from men and pre- and post-menopausal women suggested that when estrogen binds to ER-alpha, the cell is more able to break down fat. Another molecule, ER-beta, makes the cell hold fat more tightly. Women have more ER-alpha in their bellies than men do.
“We believe that keeps fat away from that fat depot,” Clegg said. “Post-menopausal women and men lack this receptor, so you get this gigantic fat depot.”
Female rats accordingly got fatter when they lacked ER-alpha. Male rats didn’t gain any weight at all.
But when Clegg and her colleagues tested the cells for obesity-related diseases like type 2 diabetes, they found that the male fat cells were alarmingly unhealthy. The cells excreted molecules that led to elevated levels of glucose and insulin, part of a condition known as the metabolic syndrome that can lead to diabetes. In addition, fat cells were shunted to the liver instead of accumulating under the skin, putting the rats at greater health risk.
“We’ve never seen such a horrible response. These males have completely unhealthy fat cells,” Clegg said. “This suggests that even in males, estrogen is important for marking the fat tissue to be relatively healthy.”