Mice experiments reveal females produce more than one protein that helps prevent non-alcoholic fatty liver disease

One of the most common disorders in the world, non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of death worldwide. Its progressive form, called “non-alcoholic steatohepatitis” (NASH), affects around 30% of all NAFLD patients, and can lead to cirrhosis and liver cancer. Despite numerous research efforts, we still do not understand the underlying mechanisms of NAFLD/NASH and therefore lack an effective treatment.

One thing we do know, however, is that it seems to be more common in men than in women, especially premenopausal women. Why this is so is not entirely clear, but current evidence suggests that estrogen, a sex hormone, plays a protective role. On the other hand, the formyl-peptide protein receptor 2 (FPR2) is known to play an important role in mediating inflammatory responses in several organs. However, no studies to date have determined its role in the liver. Could FPR2 be implicated in sex-related differences in NAFLD prevalence and severity?

Addressing this question, a research team led by Prof. Youngmi Jung from Pusan ​​National University, Korea, recently conducted a study using a mouse model, shedding light on the role of FPR2 in NAFLD/NASH and its relationship to observed sex-based differences. This work is among the very few studies of NAFLD that rely on gender-balanced animal experiments rather than the more common male-only designs. This article was posted on January 31, 2022 and was published in Volume 13, Number 578, of the journal Nature Communication on January 31, 2022.

The researchers first found that Fpr2 was highly expressed in the healthy liver of female mice. Moreover, it was expressed differently in the liver of male and female mice fed a special NAFLD-inducing diet. Silence the Fpr2 The gene made male and female mice equally vulnerable to NAFLD, suggesting that FPR2 has a protective effect on the liver.

Interestingly, the researchers also found that the production of FPR2 in the liver is mediated by estrogen. Males supplemented with external estrogen produced more Fpr2 and were more resistant to NAFLD, while females whose ovaries had been removed had reduced liver Fpr2 levels. “Taken together, our results suggest that FPR2 is a potential therapeutic target for the development of pharmacological agents to treat NAFLD/NASH,” says Professor Jung. “Furthermore, our results could aid in the development of gender-based therapies for NASH.”

This unprecedented discovery of female-specific FPR2 production in the liver and its role in NAFLD/NASH resistance will hopefully pave the way not only for new treatments, but also for a more comprehensive and gender sensitive during scientific research. In this regard, Professor Jung remarks: “Our research highlights the pressing need to design and develop better gender-balanced animal experiments, given that sex-specific expression of FPR2 in the liver had been completely overlooked. in previous studies.

Hopefully this marks the beginning of a deeper understanding of NAFLD/NASH and the first steps towards effective sex-based therapies.

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Materials provided by Pusan ​​National University. Original written by Na-hyun Lee. Note: Content may be edited for style and length.

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