Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 09, 2024 1 month, 2 weeks, 3 days, 13 hours, 22 minutes ago
Health News: In our fast-paced world, many of us reach for convenient, tasty foods that fit into our busy lifestyles. However, new research reveals that some popular dietary choices could be silently wreaking havoc on our liver health. This article breaks down the complex science behind how a high-fat and high-fructose diet can lead to severe liver dysfunction, making it easy for everyone to understand.
Proposed model of Western diet-induced liver dysfunction via epigenetic regulation. The proposed model posits that a Western diet characterized by high fructose and fat content exerts inhibitory effects on the expression of Sirt1 and Sirt7. This inhibition, in turn, reduces their deacetylation activity during histone modification. This dysregulation has a significant impact on hepatic pathogenetic progression, transitioning from the early stage of metabolic dysfunction-associated fatty liver to the more advanced state of steatohepatitis, culminating in the induction of liver fibrosis. Importantly, this series of events involves dysregulation of histone modification, specifically inhibiting G6Pase expression via promoter hyperacetylation. This inhibition of Sirt1 and Sirt7 has far-reaching implications for glucose metabolism, indicating an intermediate status that lies between steatohepatitis and liver fibrosis. The intricate interplay between dietary components, epigenetic regulation, and the consequential impact on histone modification sheds light on the potential molecular mechanisms driving the progression of liver dysfunction induced by a Western diet
Understanding MASLD: The New Name for a Common Problem
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), has become the most common chronic liver disease. This condition is closely linked to the modern Western diet, which is rich in fats and sugars, particularly fructose. With around 30% of the U.S. population affected, MASLD is a significant public health issue.
MASLD starts with the accumulation of fat in the liver, a condition known as hepatic steatosis. If left unchecked, it can progress to more severe forms, including liver inflammation and fibrosis, which can eventually lead to liver cirrhosis.
The Culprits: High Fat and High Fructose
Our study focused on the impact of a high-fat and high-fructose diet (HFHFD) on liver health using a mouse model. Previous research showed that such a diet increases body and liver weight and causes glucose intolerance and liver abnormalities. This diet-induced liver condition represents an intermediate state between fatty liver and liver fibrosis.
But why is this diet so harmful? The key lies in how these nutrients are processed in our bodies. Fructose, for example, is a sugar that is particularly effective at promoting fat production in the liver. Unlike glucose, fructose metabolism bypasses the usual regulatory steps, leading to increased fat accumulation and oxidative stress in the liver. Combined with high fat intake, this can lead to significant liver damage over time.
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The Role of Sirtuins: Guardians of Liver Health
Sirtuins are proteins that play a crucial role in regulating cellular processes, including metabolism and aging. In our study, we observed that a high-fat and high-fructose diet significantly reduced the expression of Sirt1 and Sirt7 in the liver. These proteins are known to protect against liver damage by regulating fat metabolism, reducing inflammation, and promoting the breakdown of fats.
Specifically, Sirt1 helps in reducing liver inflammation and fat accumulation. It also plays a role in preventing liver fibrosis by promoting the death of activated stellate cells, which are key players in the development of fibrosis. On the other hand, Sirt7's role is more complex, with some studies suggesting it promotes liver fat accumulation while others show it prevents liver damage. Our findings indicate that both Sirt1 and Sirt7 are crucial for maintaining liver health under a high-fat, high-fructose diet.
The Mechanism: How HFHFD Disrupts Liver Function
The study was researchers from Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station-USA that is covered in this
Health News, delved into the molecular mechanisms by which HFHFD causes liver dysfunction. We found that this diet leads to the downregulation of Sirt1 and Sirt7 at both the gene and protein levels. This disruption likely contributes to the progression of liver disease by impairing the liver's ability to process fats and sugars efficiently.
Moreover, we discovered that HFHFD also suppresses the expression of glucose 6-phosphatase (G6Pase), a key enzyme in glucose metabolism. This suppression is linked to increased acetylation of histone H3 at lysine 18 (H3K18) in the G6Pase promoter region, a change that inhibits G6Pase transcription. This epigenetic modification, driven by reduced Sirt7 activity, highlights a novel pathway through which a high-fat, high-fructose diet can promote liver fibrosis.
Implications for Public Health
The findings from our study underscore the significant impact of diet on liver health. They suggest that dietary interventions targeting the reduction of fat and fructose intake could be beneficial in preventing and managing MASLD. Given the widespread consumption of high-fat, high-sugar foods in the Western diet, these insights are particularly relevant.
Public health strategies should focus on raising awareness about the dangers of excessive fructose and fat consumption and promoting healthier dietary habits. This could include educational campaigns, food labeling reforms, and policies to reduce the availability of high-fructose foods.
Future Directions
While our study sheds light on the detrimental effects of a high-fat, high-fructose diet on liver health, more research is needed to fully understand the underlying mechanisms and to develop effective interventions. Future studies should explore the potential of targeting sirtuins and other epigenetic regulators as therapeutic strategies for MASLD.
Additionally, examining the long-term effects of dietary changes and the role of other dietary components in liver health will be crucial. Understanding the interplay between diet, genetics, and epigenetics will help in designing comprehensive approaches to prevent and treat liver diseases.
Conclusion
In conclusion, our research highlights the severe impact of a high-fat and high-fructose diet on liver health, emphasizing the role of sirtuins in mediating these effects. By understanding these mechanisms, we can better appreciate the importance of dietary choices in maintaining liver health and develop more effective public health strategies to combat the rising tide of liver disease. So next time you're reaching for that sugary snack, remember your liver and choose wisely.
The study findings were published in the peer reviewed journal: Life.
https://www.mdpi.com/2075-1729/14/6/729
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