Scientists discover why women are more resistant to nonalcoholic fatty
liver disease than men
Experiments on mice reveal that females produce more of a protein that
helps prevent nonalcoholic fatty liver disease

Date:
March 17, 2022
Source:
Pusan National University
Summary:
Nonalcoholic fatty liver disease (NAFLD) is one of the leading
causes of death worldwide. However, why premenopausal women
are more resistant to NAFLD than men is currently unknown. Now,
scientists demonstrate, through sex-balanced experiments on mice,
that the female liver produces higher levels of a protein that
has a protective effect against NAFLD. Their findings could lead
to new therapeutic strategies for treating NAFLD.



FULL STORY ==========================================================================
One of the most common disorders globally, nonalcoholic fatty liver
disease (NAFLD) is a leading cause of death worldwide. Its progressive
form, called "nonalcoholic steatohepatitis" (NASH), affects about 30% of
all NAFLD patients, and can lead to cirrhosis and liver cancer. Despite
many research efforts, we still do not understand the underlying
mechanisms of NAFLD/NASH and, consequently, lack an effective treatment.


==========================================================================
One thing we do know, however, is that it seems to be more frequent
among men than women, especially premenopausal women. Why this is
so is not entirely clear, but current evidence suggests that the sex
hormone estrogen plays a protective role. On the other hand, the protein
formyl peptide receptor 2 (FPR2) is known to play an important role in mediating inflammatory responses in multiple organs. However, no study
so far has determined its role in the liver. Could FPR2 be involved in
the sex-related differences regarding NAFLD prevalence and severity?
Addressing this question, a research team led by Professor Youngmi
Jung of Pusan National University, Korea, recently conducted a study
using mice model, shedding light on the role of FPR2 in NAFLD/NASH and
its relationship to the observed sex-based differences. This work is
among the very few studies on NAFLD that relies on sex-balanced animal experiments rather than the more common male-only designs. This paper was
made available online on 31 January 2022 and was published in Volume 13,
Issue 578, of the journal Nature Communications on 31 January 2022.

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

Interestingly, the researchers also found that FPR2 production in the
liver is mediated by estrogen. Males supplemented with external estrogen produced more Fpr2 and were more resistant to NAFLD, whereas females that
had their ovaries removed exhibited reduced liver Fpr2 levels. "Taken
together, our findings suggest that FPR2 is a potential therapeutic
target for developing pharmacological agents to treat NAFLD/NASH," says
Prof. Jung. "In addition, our results could help in the development of gender-based therapies for NASH." This unprecedented discovery of the female-specific production of FPR2 in the liver and its role in providing resistance against NAFLD/NASH will hopefully pave the way not only for
novel treatments but also a more comprehensive and sex-aware approach
when doing science. In this regard, Prof. Jung remarks, "Our research highlights the pressing need for designing and developing better sex-
balanced animal experiments, considering that the sex-specific expression
of FPR2 in the liver had been completely overlooked in previous studies."
Let us hope this marks the beginning of a deeper understanding of
NAFLD/NASH and the first steps towards effective sex-based therapies.


========================================================================== Story Source: Materials provided by Pusan_National_University. Original
written by Na-hyun Lee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Chanbin Lee, Jieun Kim, Jinsol Han, Dayoung Oh, Minju Kim,
Hayeong Jeong,
Tae-Jin Kim, Sang-Woo Kim, Jeong Nam Kim, Young-Su Seo, Ayako
Suzuki, Jae Ho Kim, Youngmi Jung. Formyl peptide receptor
2 determines sex-specific differences in the progression of
nonalcoholic fatty liver disease and steatohepatitis. Nature
Communications, 2022; 13 (1) DOI: 10.1038/s41467- 022-28138-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220317120405.htm

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