NAFLD: Mechanisms, Treatments, and Biomarkers

Abstract

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is one of the most common causes of liver diseases worldwide. NAFLD is growing in parallel with the obesity epidemic. No pharmacological treatment is available to treat NAFLD, specifically. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non-invasive biomarkers. NAFLD consists of the accumulation of excess lipids in the liver, causing lipotoxicity that might progress to metabolic-associated steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma. The mechanisms for the pathogenesis of NAFLD, current interventions in the management of the disease, and the role of sirtuins as potential targets for treatment are discussed here. In addition, the current diagnostic tools, and the role of non-coding RNAs as emerging diagnostic biomarkers are summarized. The availability of non-invasive biomarkers, and accurate and inexpensive non-invasive diagnosis tools are crucial in the detection of the early signs in the progression of NAFLD. This will expedite clinical trials and the validation of the emerging therapeutic treatments.

Association between leptin and NAFLD: A Two-Sample Mendelian randomization study

“…Therefore, the disease treatment emphasizes the regulation of metabolism, but from clinical practice, there are still several bottlenecks in NAFLD from diagnosis to treatment [9]. Firstly, in terms of diagnosis, although there are more recognized and mature protocols for monitoring NAFLD in traditional high-risk groups (diabetes, hypertension, overweight), more and more studies have found that NAFLD occurs more frequently in people with normal BMI (i.e., visceral obesity) [49], and for such patients, especially in non-obese people with intermittent transaminase abnormalities, there is still a lack of su ciently effective biological markers for the diagnosis of NAFLD and a lack of effective protocols for predicting the risk of development, as liver aspiration biopsy is still not a common tool, and current guidelines only recommend regular follow-up, which is not conducive to timely treatment [50,51]. Secondly, according to the existing guideline recommendations, lifestyle changes, exercise, and diet control are important non-pharmacological options for people with established NAFLD [52].…”

Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis

“…Histopathological evaluation using liver biopsy is the gold standard for evaluating hepatic steatosis and diagnosing NAFLD, however, this invasive diagnostic modality comes with its limitations including high cost, sampling errors, and post procedure complications [ 8 ]. Hence, multiple studies have investigated several non-invasive modalities for NAFLD diagnosis including potential biomarkers [ 9 , 10 , 11 , 12 , 13 ].…”

Thwarting Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) with Common Bean: Dose- and Sex-Dependent Protection against Hepatic Steatosis

“…MLXIPL showed a trend of inhibition in the female cohort; however, in males, was upregulated in the 70% versus 0% and 35% bean diets ( Figure 5 b). While SREBF1 is stimulated by insulin (even under conditions of insulin resistance) via mammalian target of rapamycin (mTOR) and by liver X receptor α (LXRα, encoded by Nr1h3 ), MLXIPL signaling is induced by dietary glucose (even more potently by dietary fructose) independently of insulin or dietary fat [ 33 , 34 , 35 ]. Accordingly, we observed inhibition of insulin and its receptor INSR and insulin receptor substrate 1 (IRS-1) based on bean-induced downstream DEGs indicative of improved insulin sensitivity.…”