Postmenopausal women have an increased risk of non-alcoholic fatty liver disease due to loss of estrogen due to metabolic changes. A diet high in fat further aggravates the disease, which can progress to cirrhosis and liver failure. Hormone replacement therapy (HRT) is an effective treatment, but it carries an increased risk of breast cancer, uterine cancer, and cardiovascular disease.

A research team from the University of Illinois has identified a new estrogen compound, Preferred Estrogen, that offers similar benefits to HRT but without the risk factors. In previous research, the team has shown that the compound activates specific signaling pathways, particularly in metabolic tissues.

In a new article published in nutrients, researchers are exploring the effects of preferential estrogen on liver and uterine health in mice.

Estrogens are important for the reproductive system and metabolic tissues. Hormone replacement therapy can solve some of the metabolic problems associated with the onset of menopause. But we know it also increases the risks associated with exposure to hormones. ”

Zeynep Madak-Erdogan, Associate Professor, Department of Food Sciences and Human Nutrition, U of I and lead author of the new study

“We removed the ovaries from the mice to mimic the estrogen loss that occurs in postmenopausal women. We also put the mice on a high fat diet and they gained weight fairly quickly. We treated a group of mice with hormone replacement therapy, and another group of mice with the estrogen-preferential pathway, ”says Madak-Erdogan.

The researchers observed the mice for six weeks, measuring their food intake and body composition. At the end of the trial, they took liver and uterine tissue for analysis.

Normally, estrogen causes an increase in uterine weight, but that did not happen with preferential estrogen. This is a good thing, because it suggests that there are no negative effects. on the uterus, ”says Madak-Erdogan.

Treatment with estrogen or preferred estrogen can help reduce excessive lipid deposition in the liver. This was already known, says Madak-Erdogan.

“What’s new in this article is that we used genomic sequencing. We specifically looked at the changes in liver cells with the addition of the preferred estrogen pathway, and how that compares to what happens. happens when you give estrogen, ”she notes.

“We found that there was an increase in the generation of new mitochondria with preferential estrogen. Mitochondria are a powerhouse and you need new, healthy mitochondria so that your cells can continue to function. This is especially important for liver cells, hepatocytes. “

As a result, even though the mice were getting more calories, they also burned more when they were given preferential estrogen. The compound can also prevent the progression of fibrosis.

“As nonalcoholic fatty liver disease progresses from lipid deposition to cirrhosis, it damages the liver cells more and fibrosis begins. As you accumulate more lipids, it will cause oxidative stress. and will begin to damage the hepatocytes, ”said Madak-Erdogan explains.

“When we treated the animals with the preferred estrogen, the reduction in fibrosis was much greater than that of estrogen. The compound causes higher utilization of what comes from the diet, but it also protects against damage. by over-dieting itself and by the deposition of lipids.This means that preferential estrogen prevents further fibrosis, which is the pathway that leads to liver failure and metabolic problems.

The pathway’s preferred estrogen is structurally estrogen, functioning by uptake of estrogen receptors, but due to the compound’s unique properties, it improves liver health without causing additional risk to reproductive tissues, the researchers note. .

John Katzenellenbogen, U of I chemistry research professor, developed the estrogen-preferential pathway in his research lab. Testing for the compound is still in the preclinical stage, and researchers continue to observe its effects on body tissue in animal studies.


University of Illinois College of Agricultural, Consumer, and Environmental Sciences

Journal reference:

Zuo, Q., et al. (2021) Pathway Preferred Estrogens Prevent Hepatosteatosis Due to Oophorectomy and High Fat Diets. Nutrients.

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