New Research Explains Why Low Estrogen Leads To Risk For Diabetes And Cardiovascular Disease

Dec 6, 2017

Dr. Maria Torres published a study that helps explain the link between cell mitochondria and a risk for diabetes and cardiovascular disease in middle age women.
Credit Cliff Hollis - ECU News Services

Local research is changing the way we understand insulin resistance and problems with metabolism in middle age.  Dr. Maria Torres sheds new light on cell mitochondria and its impact on cardiovascular disease and diabetes, especially in women.

The study by post-doctoral scholar at the East Carolina Diabetes and Obesity Institute in Greenville Dr. Maria Torres was published last month in the respected publication Cell Metabolism.  Torres moved from Uruguay to the United States to pursue her PhD in 2012. 

“Back at home, I was a biochemist and a fitness instructor.  So my life was like in a lab and in the gym.”

Torres’ scientific curiosity was sparked through conversations with women concerned about staying healthy as they aged.

“I kept remembering all of my students in my gym classes and my fitness group classes, they were all women ranged between 20 to 70, I had all of them.  And every single one of them mentioned at some point mentioned menopause and how they were still in the same diet they were still exercising and they were gaining weight.  They were like, what’s going on, why am I gaining weight?”

After five years of research, Torres is now able to answer that question.  It starts with understanding the role of mitochondria in cellular function. 

“They are these small engines like in your car that turn the energy you get from the foods you eat into a form of energy that the body can use.  The flow of energy through that engine depends on a lot of components and if something goes wrong in that engine, just like in a car, you lose performance, you lose efficiency.”

Credit Cliff Hollis - ECU News Services

One of the components of the mitochondrial inner membrane is estrogen.  Since the presence of the hormone is greatly reduced during menopause, this affects the overall function of the powerhouses of the cell - mitochondria.

“What we’re proposing is these engines are used to running on a certain level of estrogen in their membranes and it promotes this bioenergetics efficiency. Now, that content of estrogen is lost because the ovaries stop producing it.  So what happens to that engine?  It’s like when you have the oil light on in your car and you’re not paying attention to it.”

The amount of estrogen present in the mitochondrial membrane affects its pliancy.  More estrogen means the mitochondria membrane is more fluid and the “engines” are able to better respond to the need for energy.  But as estrogen is reduced and the membrane becomes more ridged, it inhibits the ability for mitochondria to maintain energy charge. Torres says estrogen directly changes the efficiency of electron transfer in the electron transport system.

“In the mitochondria, you have all these transporters/proteins that just pump electrons from one to the next, to the next.  It’s literally like electricity going through it.  And how that membrane is assembled directly alters the function of those proteins of those pumps.  So we are proposing that estrogen can be a key component of that mitochondrial membrane and can directly affect the efficiency of the whole engine.”

Until now, conventional wisdom has been that estrogen was always working through receptors specific to estrogen.  Torres’ new findings further explain that the hormone is actually a key component of mitochondrial function and can directly affect the efficiency of the whole engine. 

“I think what our paper is bring is getting a little bit more light into that part… into that mode of action of estrogen that is nongenomic and is estrogen receptor independent which nobody has known. 

Dr. Maria Torres, left, prepares equipment in the lab on the fourth floor of the East Carolina Heart Institute as Dr. Darrell Neufer, director of the East Carolina Diabetes and Obesity Institute, observes.
Credit Cliff Hollis - ECU News Services

Understanding how the mitochondrial membrane might be modulated could lead to the development of safer hormone replacement therapies specifically targeting the mitochondrial inner membrane.

We could be opening a lot of doors in research.  For example, the first thing that I can think of is let’s develop a pharmacological agent that can go in there, get in the mitochondrial membrane and fix everything that estrogen was doing when it was there without binding to all the estrogen receptors and having potential detrimental oncogenic effects.”

There may be applications of this research beyond women’s health. Torres explains testosterone like estrogen comes from cholesterol, a key component of membranes.  Cholesterol acts like a glue and holds lipids together. 

“Estrogen has the same structure only with a tiny, tiny difference that makes it completely opposite from cholesterol.  So if cholesterol glues everything and holds everything tight, estrogen does the complete opposite.  And it makes the membrane less fluid or less viscus. So if it is strictly related to a structure, then the question becomes what about all of these steroid hormones?  Right?  Could these be applicable to all these others, could this also explain why testosterone affects insulin sensitivity?  Potentially.”

To view Dr. Maria Torres' study published November 2nd in Cell Metabolism, go to: http://www.cell.com/cell-metabolism/abstract/S1550-4131(17)30615-0