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The following article was published in our article directory on April 11, 2022.
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Why are women less likely to develop nonalcoholic steatohepatitis?

Article Category: Wellness, Fitness and Diet

Author Name: Candy Swift

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases and one of the leading causes of death worldwide. Its progressive form, known as nonalcoholic steatohepatitis (NASH), affects approximately 30% of people with NAFLD and can lead to cirrhosis and liver cancer. Despite multiple studies, we still do not fully understand the underlying mechanisms of NAFLD/NASH and therefore lack effective treatments.

What we do know, however, is that NAFLD is more common in men, but the exact reasons behind this are still not fully understood. Previous studies have suggested that estrogen may play a protective role. In addition, formyl peptide receptor 2 (FPR2) plays an important role in mediating inflammatory responses in several organs, but it is unclear whether FPR2 plays a role in the liver or whether it is associated with the prevalence of NAFLD and gender differences.

Recently, researchers from Pusan National University in Korea published a paper in Nature Communications titled "Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis".

The protective role of FPR2 in the liver, whose expression is mediated by estrogen, was confirmed by mouse model studies, suggesting that FPR2 is a potential target for the development of drugs to treat NAFLD/NASH, and these findings could contribute to the development of gender-based therapies for NAFLD/NASH.

The team first found that FPR2 was highly expressed in the healthy livers of female mice. In addition, FPR2 was differentially expressed in female and male mice with NAFLD induced by high-fat diet feeding. Female and male mice were equally susceptible to NAFLD after silencing the FPR2 gene, and these findings suggest that FPR2 has a protective effect on the liver.

The researchers also discovered that the estrogen estradiol mediated the high expression of FPR2 in the liver, and that male mice supplemented with estradiol produced more FPR2 and were thus more resistant to NAFLD, whereas female mice with ovaries removed had lower levels of hepatic FPR2 expression.

FPR2 is a viable therapeutic target for the development of drugs to treat NAFLD/NASH, according to researchers.

The production of female-specific FPR2 in the liver and its role in anti-NAFLD/NASH is expected to pave the way not only for new therapeutic approaches but also for more comprehensive and gender-specific approaches when conducting scientific research, according to the study's corresponding author, Professor Young-Mi Chung. This study also highlights the urgent need to design and develop better gender-balanced animal experiments, as previous studies have completely ignored the gender-specific expression of FPR2 in the liver.

She also stated that the research is the first step toward a better knowledge of NAFLD/NASH and the first step toward effective gender-based therapies.

Keywords: NAFLD related protein study, membrane protein

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