New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut–Liver–Heart Crosstalk

Abstract

Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut–liver–heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut–liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host–microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut–liver–heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut–liver–heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.

Transforming Screening, Risk Stratification, and Treatment Optimization in Chronic Liver Disease Through Data Science and translational Innovation

“…Metabolic dysfunction underlies the pathogenesis of metabolic-associated fatty liver disease (MAFLD), encompassing interlinked factors like aberrant lipid metabolism, insulin resistance, and diabetes. 24 Its development implicates numerous interlinked factors including oxidative stress, derangements in lipid metabolism, insulin resistance, inflammation, gut microbiota imbalance, and immune dysregulation. The interplay of these molecular aberrations and systemic metabolic abnormalities contributes to hepatic lipotoxicity, activation of fibrogenic pathways, and cumulative liver damage as depicted in Figure 1.…”

The Liver in Heart Failure: From Biomarkers to Clinical Risk

“…Therefore, it is appropriate in the clinical assessment of patients with suspected CH to investigate the presence of comorbidities that may have caused or contributed to CLD before or along with heart disease [30]. It appears mandatory in such patients to exclude the presence of chronic viral infections (HBV; HCV), to assess the extent of alcohol consumption, to exclude storage diseases (hemochromatosis) or autoimmune liver diseases, and to assess the presence of metabolic comorbidities underlying steatohepatitis (diabetes, hypertension, and obesity) [31].…”

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

“…The pathology of metabolic disorders involves an intricate interplay between oxidative stress and chronic inflammation, which leads to atherosclerosis, tissue fibrosis, and cardiovascular disease [ 13 ]. Additionally, they are increasingly prevalent and have emerged as global health challenges posing a serious threat to global health [ 14 , 15 ].…”