Los estrogens play a key role in women’s health, since these hormones help protect women’s hearts, however, estrogen levels drop after menopause and this increases the chances of developing various pathologies, including diabetes, obesity and heart disease.
A group of scientists from the Baker Heart and Diabetes Institute has identified a receptor for sex hormones in the heart of mice that has the ability to regulate adiposity or accumulation of body fat and could help regulate weight in postmenopausal women for prevent obesity.
Their findings have been published in Nature Cardiovascular Research and show that the decreased estrogen receptor alpha (ERα) in the cells responsible for the heart’s contraction (cardiomyocytes) led to moderate cardiac dysfunction and increased obesity rates in female mice, but not in male mice. This sex hormone receptor in the heart can regulate adiposity in womenaccording to Professor Julie McMullen of the Baker Heart and Diabetes Institute.
The results of this research have important implications for the prevention and treatment of cardiac and metabolic diseases in postmenopausal women.
“We have been interested in trying to understand the role of this estrogen receptor in the heart for some time, to see how it protects the heart”. “When we blocked this estrogen receptor, we expected to see changes and damage primarily in the heart. But instead of seeing a dramatic cardiac phenotype, what we saw was an adiposity phenotype. So, we observed that the female mice weighed more and had more fat mass, which we did not expect at all”, she explained.
Genes relevant to the heart’s contractility and metabolic function were also lower in the female heart when ERα was lowered, which explains why the female hearts in the study did not pump as well. David Greening, associate professor of extracellular vesicle biology at La Trobe University, explained that the particles – called extracellular vesicles – that were released from ERα-reduced female hearts also contained different proteins from both the control group and the male hearts.
“We found that ERα reduction in female mouse cardiac muscle cells (cardiomyocytes) leads to transcriptional, lipidomic, and metabolic dysregulation in the heart, along with metabolic dysregulation in skeletal muscle and adipose tissue,” Greening says.
“In addition, the extracellular vesicles that are released from ERα-reduced heart cells had the ability to reprogram skeletal muscle cells in cell culture. These changes in the tissues, extracellular vesicle proteome, and reprogrammed skeletal muscle cells altered the molecular landscape and function of the cells. So, instead of expending energy, energy is stored, which explains the increase in adiposity in female mice in the absence of Erα,” adds Greening.
Prevent heart and metabolic diseases after menopause
The results of this research have important implications for the prevention and treatment of cardiac and metabolic diseases in postmenopausal women, and may also contribute to reduce cardiotoxicity in premenopausal women receiving therapies that can inhibit or reduce ERα in the heart.
“Women taking drugs that can interact with or inhibit this particular receptor, including some chemotherapies, often become obese,” says Professor McMullen. “Now that we have a better understanding of ERα, we have a better chance of identifying therapies for prevent the development of obesity”.
Associate Professor Greening concludes that this study has shown that “extracellular vesicles, nanovesicles with their packed molecular cargo, are systemic signaling regulators that can travel to and impact other organs in the body, including adipose tissue and skeletal muscle.” “Extracellular vesicles thus provide a new paradigm in crosstalk between cells, tissues, and organs in health and disease.”