Abstract
The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.
Highlights
The prevalence of NAFLD is a rapidly increasing problem, affecting 25–45% of the adult population worldwide and up to 70% in T2DM and obesity patient groups [1]
We focus on the role of liver lipid homeostasis and mitochondrial β-oxidation in the connection between NAFLD and CVD, associated genetic regulations, and targeted therapies
The described cold-adaptation-related role of perilipin 5 (Plin5) implies a role of the homeostasis and thermogenesis of liver lipids in NAFLD development [106]. These findings elucidate that PLIN5 is a crucial pleiotropic regulator of hepatic lipid metabolism, thermogenesis, and inflammatory response involved in NAFLD/NASH and atherosclerosis development and progression
Summary
The prevalence of NAFLD is a rapidly increasing problem, affecting 25–45% of the adult population worldwide and up to 70% in T2DM (type 2 diabetes mellitus) and obesity patient groups [1]. The level of fetuin-A was linked to hypertriglyceridemia, and there was no significant association with risk of ischaemic stroke and other CVD [35], while other research suggests it as a valuable factor for chronic heart failure diagnostics [36]. Different extents of dyslipidemia often present in NAFLD/NASH patients (decreased level of HDL-C, and increased levels of LDL particles and TG (triglycerides)), and serve as an important non-invasive marker for NAFLD diagnostics [27,37] Such a lipid profile is known as atherogenic and was linked with the severity of cardiometabolic risk [38,39]. We focus on the role of liver lipid homeostasis and mitochondrial β-oxidation in the connection between NAFLD and CVD, associated genetic regulations, and targeted therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
