Impact of NAFLD and its pharmacotherapy on lipid profile and CVD.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Increasing evidence suggests that, in addition to traditional metabolic risk factors such as obesity, hypercholesterolemia, hypertension, diabetes mellitus, and insulin resistance (IR), nonalcoholic fatty liver disease (NAFLD) is an emerging driver of ASCVD via multiple mechanisms, mainly by disrupting lipid metabolism. The lack of pharmaceutical treatment has spurred substantial investment in the research and development of NAFLD drugs. However, many reagents with promising therapeutic potential for NAFLD also have considerable impacts on the circulating lipid profile. In this review, we first summarize the mechanisms linking lipid dysregulation in NAFLD to the progression of ASCVD. Importantly, we highlight the potential risks of/benefits to ASCVD conferred by NAFLD pharmaceutical treatments and discuss potential strategies and next-generation drugs for treating NAFLD without the unwanted side effects. [Display omitted] • Nonalcoholic fatty liver disease has emerged as a driver of atherosclerotic cardiovascular disease. • Acetyl-coenzyme A carboxylase inhibitors and farnesoid X receptor agonists disrupt the circulating lipid profile, which may increase the risk of atherosclerotic cardiovascular disease. • A novel molecule, IMA-1, moderately represses acetyl-coenzyme A carboxylase 1 activity and has promising potential in treating nonalcoholic steatohepatitis without causing a significant decrease in polyunsaturated fatty acid levels or hyperlipidemia. [ABSTRACT FROM AUTHOR]