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Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation.

ABSTRACT: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

SUBMITTER: Carnagarin R

PROVIDER: S-EPMC8073135 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAs fat and obesity play a vital role in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD), this study aims to investigate the association between the fat mass and obesity-associated gene (FTO) and MAFLD.MethodsSix SNPs (rs6499640, rs1421085, rs8050136, rs3751812, rs9939609 and rs9930506) within FTO were genotyped for 741 MAFLD patients (median age, 69.98; interquartile range, 66.55-75.93) and 825 healthy people (median age, 69.94; interquartile range, 66.39-75.64). Allele and genotype frequencies, pairwise linkage disequilibrium (LD) and haplotype analysis were calculated.ResultsBMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride, alanine transaminase, glutamyl transpeptidase and the prevalence of diabetes were found to be higher in the MAFLD individuals comparing to the control ones (P < 0.05). For rs1421085, the C allele frequency was remarkably higher in MAFLD after Bonferroni correction (OR [95% CI] =1.353 [1.095-1.671]; P corr =0.030), and a significantly different genotype result was observed in log-additive model (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024). For rs8050136, significantly increased A allele frequency was observed in MAFLD (OR [95% CI] =1.371 [1.109-1.695]; P corr =0.024), and A-allele carriers showed increased MAFLD risk (OR [95% CI] =1.393 [1.103-1.759]; P corr =0.030). For rs3751812, the T allele frequency was remarkably higher in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and T-allele carriers demonstrated high MAFLD risk (OR [95% CI] =1.392 [1.103-1.756]; P corr =0.030). For rs9939609, A allele frequency was also remarkably high in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and A-allele carriers were more susceptible to MAFLD (OR [95% CI] =[1.103-1.756]; P corr =0.030). A strong LD was found among rs1421085, rs8050136, rs3751812 and rs9939609 (r2 >0.8), and individuals with C-A-T-A haplotype had an elevated MAFLD risk (P =0.005).ConclusionThe case-control study indicated that C variant of rs1421085, A variant of rs8050136, T variant of rs3751812 and A variant of rs9939609 are associated with elevated MAFLD risk in the older Chinese Han population.

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Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation.

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