2. Molecular mechanism of regulating glucose and lipid metabolism in liver
1) Characterization of novel pathways of promoting Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
♦ What is Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?
Obesity has emerged as a host of metabolic disorders, such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Many reports have demonstrated that 90% of obese patients in the United States have MASLD ranging from hepatic steatosis to much more severe forms of Metabolic Dysfunction-Associated Steatohepatitis(MASH), which can induce fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). MASLD is associated with hepatic metabolic reprogramming that leads to excessive lipid accumulation and imbalances in lipid metabolism in the liver. Hepatic lipid homeostasis is appropriately described as a complex machinery involving signaling and transcriptional pathways, as well as targeted genes associated with fatty acid (FA) oxidation and lipogenesis. Although the pathogenesis of MASLD has been widely studied for years, the molecular mechanisms underlying its complicated disorder are still being investigated.
♦ Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in MASLD remain largely unclear. MicroRNAs (miRNAs) are short, non-coding RNA molecules with a length of 18-25 nucleotides that play an important role in regulating the expression of target genes in a post-transcriptional manner by targeting base-pairing with the 3’-UTR of specific target mRNAs, inhibiting translation, or mRNA degradation. These miRNAs contribute to the regulation of a wide variety of cellular functions and metabolic homeostasis, including fatty acid metabolism. Recent studies have suggested that miRNAs significantly regulate the pathogenesis of MASLD by targeting the nuclear receptors (eLife 2021). Using network analysis and functional genomic approaches to determine the correlation between NRs and microRNA in MASLD patients, we are trying to identify the crucial miRNAs which are specifically regulate the progress of MASLD.