Amazing discovery! Fathers drinking coffee can cause fatty liver disease in their offspring

Author: Huang Yanhong Duan Yuechu

In the vast field of medical and biological research, every new discovery is like throwing a boulder into the ocean of knowledge, stirring up waves. Recently, a research result of Wang Hui's team at Wuhan University has attracted widespread attention in the scientific community. Their research paper was published in the journal Advanced Science, revealing a shocking phenomenon: fathers' coffee drinking can be inherited across generations, causing their offspring to suffer from fatty liver.

1. Research Background

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver metabolic disease worldwide, affecting approximately 30% of the population. Among them, non-alcoholic steatohepatitis (NASH) is a serious progressive form of NAFLD. The pathogenesis of NAFLD involves a complex interaction of genetic susceptibility, environmental factors, and metabolic stress.

The "Developmental Origins of Health and Disease Theory (DOHaD)" points out that metabolic diseases in adults may originate in the fetal period, and adverse environmental factors during embryonic development can lead to metabolic adaptation and permanent changes in offspring, increasing their risk of various metabolic diseases after birth. The paternal origin of health and disease theory (POHaD), which has been widely studied in recent years, emphasizes that unhealthy lifestyles and environmental exposures from fathers are important independent risk factors for abnormal development and disease in children. Epidemiological data show that people whose fathers have experienced famine have a significantly increased risk of obesity and diabetes. Clinical and experimental studies have also found that fathers' exposure to adverse environmental factors before pregnancy, such as smoking, high-fat diets, and chronic stress, can lead to intrauterine growth restriction and lipid metabolism dysfunction after birth, highlighting the important role of the father's pre-pregnancy environment in making offspring susceptible to a variety of diseases (including NAFLD).

2. Research Methods

1. Establishment of rat model

The research team established a paternal pre-pregnancy caffeine exposure (PPCE) rat model, giving male rats 15-60 mg/kg body weight of caffeine per day by gavage for 8 consecutive weeks, and then allowed these male rats to mate with female rats and produce offspring.

2. Multi-faceted analysis

The offspring rats were subjected to a variety of analyses, including observing whether they developed symptoms of non-alcoholic steatohepatitis (NASH), detecting the expression levels of related genes and molecules, and exploring changes in sperm epigenetic modifications.

3. Research Results

1. Transgenerational NASH

Results: Male offspring of rats with paternal pre-pregnancy caffeine exposure (PPCE) exhibit transgenerationally inherited nonalcoholic steatohepatitis (NASH) in adulthood.

2. The key role of miR-142-3p

Mechanistically, a reduction in one miRNA, miR-142-3p, has been implicated in the development of nonalcoholic steatohepatitis (NASH). NASH is characterized by dysfunctional hepatic lipid metabolism and chronic inflammation resulting from elevated ACSL4 expression in the liver. The source of the reduction in miR-142-3p is hypermethylation of the promoter region of miR-142-3p in paternal sperm, which is caused by high levels of corticosterone (a member of the glucocorticoid family) rather than by caffeine itself. Similar results were seen in offspring conceived through in vitro fertilization using sperm from miR-142-3p knockout.

4. Research Conclusions and Implications

1. Provide the first evidence

This study provides the first evidence for transgenerational inheritance of nonalcoholic steatohepatitis (NASH) in offspring of paternal preconception caffeine exposure (PPCE).

2. Identify potential therapeutic targets

We identified miR-142-3p as a potential therapeutic target for NASH caused by adverse paternal environmental factors.

3. Provoke thinking

This research result has triggered a deep reflection on people's eating habits in daily life. Caffeine is a central nervous system stimulant commonly found in a variety of beverages and foods such as coffee, tea, chocolate and soft drinks. Its potential impact on male reproductive health and the health of offspring cannot be ignored. During the reproductive period, men tend to consume more caffeine than women, which further highlights the need to pay attention to the potential risks of fathers' caffeine intake to the health of their offspring.

4. Expand research directions

This study not only provides a new direction for the study of non-alcoholic steatohepatitis, but also provides an important reference for understanding other transgenerational genetic diseases caused by environmental factors. Future studies can further explore the role of miR-142-3p in other diseases and how to prevent and treat transgenerational genetic diseases by intervening in sperm epigenetic modifications.

In short, the research results of Wang Hui's team at Wuhan University have opened a new window for us to understand transgenerational genetic diseases. It reminds us that the father's lifestyle and environmental exposure may have a profound impact on the health of future generations. In daily life, we should pay more attention to the potential impact of diet and lifestyle habits on health, especially for people who are preparing to have children, they should choose their diet and lifestyle carefully to reduce potential risks to the health of future generations. I believe that in the future, with the continuous deepening of scientific research, we will be able to better understand and prevent transgenerational genetic diseases and bring more protection to human health.