In recent years, there has been a growing concern about the impact of chronic illness on our long-term health. Among the various organs affected by these conditions, the liver plays a crucial role.
One condition that has garnered significant attention is fatty liver disease. Although commonly associated with excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD) has emerged as a serious health concern.
In this article, we will delve into the relationship between fatty liver and long-term health problems, shedding light on this liver-chronic illness nexus.
Understanding Fatty Liver Disease:
Fatty liver disease is characterized by the accumulation of fat in liver cells. This condition is commonly associated with:
- Obesity
- Diabetes
- Metabolic syndrome
Although it can also occur in individuals who are not overweight. When left untreated, fatty liver disease can progress from simple steatosis (excessive fat accumulation) to a more severe condition known as non-alcoholic steatohepatitis (NASH), which is marked by liver inflammation and potential scarring.
The Link with Chronic Illness:
While fatty liver disease may seem like a localized concern, recent studies have revealed a significant association between this condition and long-term health problems.
The liver acts as a metabolic hub, playing a vital role in various physiological processes, including glucose regulation, lipid metabolism, and detoxification. When the liver is burdened with excessive fat, it can lead to a cascade of detrimental effects throughout the body.
Insulin Resistance and Type 2 Diabetes:
Fatty liver disease has been strongly linked to insulin resistance, a condition in which the body’s cells become less responsive to insulin. Insulin resistance often precedes the development of type 2 diabetes, a chronic illness that affects millions of people worldwide.
The accumulation of fat in the liver contributes to systemic inflammation and disrupts insulin signaling, leading to elevated blood sugar levels and the onset of diabetes.
The relationship between fatty liver and insulin resistance/type 2 diabetes is complex and multifactorial. Here are some key mechanisms that explain how fatty liver contributes to the development of insulin resistance and type 2 diabetes:
Increased release of free fatty acids (FFAs): In fatty liver, there is an increased release of FFAs from the liver into the bloodstream. These FFAs can impair insulin signaling in various tissues, including the liver itself, muscle, and adipose tissue.
The presence of excess FFAs leads to insulin resistance by interfering with the normal insulin-mediated glucose uptake and utilization in these tissues.
Inflammation and cytokine release: Fatty liver is associated with a low-grade chronic inflammation in the liver called non-alcoholic steatohepatitis (NASH).
Inflammatory cells release cytokines and other inflammatory molecules that can disrupt insulin signaling pathways in the liver and other tissues. These inflammatory molecules contribute to the development of insulin resistance.
Alteration of adipokine secretion: Fatty liver can alter the secretion of adipokines, which are hormones secreted by adipose tissue. Adipokines play a role in regulating insulin sensitivity.
In fatty liver, there is an imbalance in adipokine production, with increased release of pro-inflammatory adipokines (such as tumor necrosis factor-alpha or TNF-alpha) and decreased secretion of anti-inflammatory adipokines (such as adiponectin). This imbalance further promotes insulin resistance.
Increased hepatic glucose production: Fatty liver is associated with increased hepatic (liver) glucose production. Normally, the liver plays a crucial role in maintaining blood sugar levels by producing glucose when needed and storing excess glucose as glycogen.
However, in fatty liver, the liver becomes less responsive to the inhibitory effects of insulin on glucose production. This leads to excessive glucose release into the bloodstream, contributing to high blood sugar levels and insulin resistance.
It’s important to note that while fatty liver can contribute to the development of insulin resistance and type 2 diabetes, not everyone with fatty liver will develop these conditions.
Cardiovascular Disease:
The liver-chronic illness nexus extends to cardiovascular health as well. Fatty liver disease is associated with an increased risk of developing heart disease, including conditions like hypertension, atherosclerosis, and heart attacks.
Firstly, fatty liver disease is often associated with insulin resistance, a condition in which the body’s cells become less responsive to the hormone insulin. Insulin resistance can lead to high blood sugar levels and an increased risk of developing type 2 diabetes.
Diabetes, in turn, is a significant risk factor for cardiovascular disease. It can damage the blood vessels and increase the likelihood of plaque formation, leading to conditions like atherosclerosis and heart disease.
Secondly, fatty liver disease is closely related to an imbalance in blood lipid levels, particularly elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often referred to as “good” cholesterol.
High triglycerides and low HDL cholesterol are both risk factors for cardiovascular disease. These lipid abnormalities can promote the development of atherosclerosis, a condition in which fatty deposits build up in the arteries and restrict blood flow to the heart and other organs.
Furthermore, chronic inflammation is a common feature of fatty liver disease. The liver, when overwhelmed by excess fat, can release inflammatory substances that circulate throughout the body.
Chronic inflammation plays a significant role in the development and progression of cardiovascular disease. It can lead to endothelial dysfunction, a condition in which the inner lining of blood vessels becomes impaired, promoting plaque formation and narrowing of the arteries.
Chronic Kidney Disease:
Emerging evidence suggests a relationship between fatty liver disease and chronic kidney disease (CKD). Studies have shown that individuals with NAFLD have an elevated risk of developing CKD, independent of traditional risk factors such as obesity and diabetes. Shared metabolic pathways, oxidative stress, and chronic inflammation are believed to contribute to this association.
Fatty liver disease, also known as hepatic steatosis, occurs when there is an abnormal buildup of fat in the liver cells. This can happen due to various reasons such as obesity, excessive alcohol consumption, certain medications, or certain medical conditions.
Fatty liver disease itself does not usually cause symptoms and is often reversible with lifestyle changes. However, if left untreated, it can progress to a more severe form called non-alcoholic steatohepatitis (NASH), which can lead to liver inflammation, scarring, and ultimately liver damage or cirrhosis.
Chronic kidney disease (CKD) is a condition in which the kidneys gradually lose their ability to function properly. It can be caused by various factors, including high blood pressure, diabetes, autoimmune diseases, genetic disorders, and certain infections.
CKD progresses in stages, starting with mild kidney damage and gradually worsening over time. In the advanced stages, it can lead to kidney failure, where the kidneys are no longer able to filter waste and toxins from the blood effectively.
Although fatty liver disease itself doesn’t directly cause chronic kidney disease, both conditions share some common risk factors, such as obesity, diabetes, and high blood pressure. These risk factors can independently contribute to the development of both fatty liver disease and chronic kidney disease.
Obesity, for example, can increase the risk of developing fatty liver disease and also puts strain on the kidneys, leading to kidney damage over time. Similarly, conditions like diabetes and high blood pressure can damage both the liver and the kidneys independently.
Liver Cirrhosis and Hepatocellular Carcinoma:
For some individuals, fatty liver disease can progress to a more severe condition known as NASH, which can lead to liver cirrhosis and hepatocellular carcinoma (HCC).
Liver cirrhosis involves the irreversible scarring of liver tissue, compromising its ability to function properly. HCC, the most common type of liver cancer, has been strongly linked to NASH.
The increasing prevalence of fatty liver disease raises concerns about the long-term impact on liver health and the potential for liver-related complications.
Conclusion
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References
Samuel, V. T., & Shulman, G. I. (2018). Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. Cell metabolism, 27(1), 22–41. https://doi.org/10.1016/j.cmet.2017.08.002
Dam-Larsen, S., Franzmann, M., Andersen, I. B., Christoffersen, P., Jensen, L. B., Sørensen, T. I., Becker, U., & Bendtsen, F. (2004). Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut, 53(5), 750–755. https://doi.org/10.1136/gut.2003.019984
Nivukoski, U., Niemelä, M., Bloigu, A. et al. Combined effects of lifestyle risk factors on fatty liver index. BMC Gastroenterol 20, 109 (2020). https://doi.org/10.1186/s12876-020-01270-7
