A new study by researchers at Cornell University in the United States has revealed promising pathways that increase our understanding of how healthy and unhealthy fat tissue develop from stem cells, which may one day help tackle the obesity epidemic. The study also advances our understanding of how unhealthy white fat can be reduced in postmenopausal women.
estrogen hormone
Researchers have known for years that sex hormones—testosterone and estrogen—play a role in regulating fat development. Estrogen normally facilitates the formation of “healthy” subcutaneous fat, which provides protection.
When estrogen is removed, as during menopause, women lose their “healthy” fat and gain “unhealthy” white fat, which is where excess calories are stored. This is why women develop heart disease and metabolic disease in their 50s. Metabolic disease is any disease or disorder that disrupts the normal metabolic process in which food is converted into energy at the cellular level.
The decline in estrogen during menopause leads to changes in body fat distribution and associated cardiovascular and metabolic diseases. Under normal circumstances, estrogen therapy requires high doses to be effective, which also increases the risk of breast cancer.
But the results of a new study, published August 5 in the journal Nature Communications, identify potential treatments that may one day reverse these unhealthy changes.
Evil Future
A protein sits on the outer membrane of cells, forming a receptor known as Cxcr4. This receptor is known for its ability to attract and retain stem cells in the microenvironment as they mature.
These stem cells can become different types of tissue. Some of these cells receive signals and commit to becoming fat cells. This process, in which a stem cell commits to becoming a fat cell, is called “adipogenesis.” The adipogenesis is the history of a cell from when it was a stem cell to when it became a fat cell.
Researchers found that inhibiting the CXCR4 receptor in mice reduced the tendency of fat stem cells to turn into white fat, also known as white adipose tissue.
The research team used an engineered mouse that allowed them to delete CXCR4 in this fat strain, thereby removing the receptor. They found that when the receptor was deleted, male mice had a slight reduction in white adipose tissue. But when they examined females of the same generation, they found no white adipose tissue.
Knowing that CXCR4 regulates stem cell biology, the researchers next examined whether deleting the receptor made the stem cells more or less committed to becoming white fat cells.
“When we deleted CXCR4, we found that the stem cells were less committed to the fat lineage in female mice and appeared more sensitive to estrogen treatments,” said Daniel Perry, assistant professor of nutritional sciences at the College of Human Ecology at Cornell University in the United States.
Low dose estrogen therapy
This finding suggests that lower doses of estrogen therapy may be effective in the absence or pharmacological inhibition of CXCR4.
To test this, the team removed the ovaries, which produce estrogen, from these female mice. “We noticed that the fat came back when we removed the estrogen from their bodies,” Perry said, according to EurekAlert.
Researchers believe that by blocking CXCR4, followed by low-dose estrogen therapy, the harmful side effects of breast cancer could be reduced. The treatment may also protect against heart disease and metabolic diseases associated with excess white adipose tissue.
“We are beginning to understand how fat is formed between males and females, and this allows us to think differently about the obesity epidemic,” Perry said.