Study Sheds Light on Role of Sex Hormones in Weight Gain and Cardiometabolic Health

A decrease in estrogen during menopause leads to alterations in body fat distribution and an increased risk of cardiovascular and metabolic diseases. However, a recent study has uncovered potential treatments that could eventually reverse these adverse changes.

A study published in Nature Communications suggests that blocking a receptor known as Cxcr4 in mice decreases the likelihood of fat stem cells becoming white fat, or white adipose tissue. This approach could be used alongside low doses of estrogen therapy to help manage changes in body fat distribution in menopausal women and reduce the risk of cardiometabolic diseases. Typically, effective estrogen therapy requires higher doses, which increases the risk of breast cancer.

Researchers have long understood that sex hormones like testosterone and estrogen influence fat development. Estrogen typically promotes the accumulation of beneficial subcutaneous fat, which offers metabolic protection. However, when estrogen levels drop, such as during menopause, women lose this protective fat and instead gain unhealthy white fat, which stores excess calories. This shift often leads to an increased risk of cardiometabolic diseases in women as they reach their 50s.

This discovery opens up exciting possibilities for exploring how healthy and unhealthy fat tissues form stem cells, potentially aiding efforts to combat obesity. It also suggests a strategy for reducing unhealthy white fat in postmenopausal women by blocking Cxcr4 and then using low-dose estrogen therapy, which could minimize the risk of breast cancer. Such an approach might also help prevent cardiovascular and metabolic diseases linked to excess white fat.

Reference: Steiner, B.M., Benvie, A.M., Lee, D. et al. Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner. Nat Commun 15, 6622 (2024). https://doi.org/10.1038/s41467-024-50985-8