Alcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to
alcoholic liver disease (ALD). With the continued
ethanol consumption,
alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including
alcoholic steatohepatitis,
fibrosis/
cirrhosis, and even eventually progress to
hepatocellular carcinoma and
liver failure. Furthermore, cell
trauma,
inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of
ethanol-mediated liver lesions. AFLD is characterized by excessive fat deposition in liver induced by excessive drinking, which is related closely to the raised synthesis of
fatty acids and
triglyceride, reduction of mitochondrial
fatty acid β-oxidation, and the aggregation of
very-low-density lipoprotein (VLDL). Although little is known about the cellular and molecular mechanisms of AFLD, it seems to be correlated to diverse signal channels. Massive studies have suggested that
liver steatosis is closely associated with the inhibition of silent information regulator 1 (
SIRT1) and the augment of lipin1 β/α ratio mediated by
ethanol. Recently,
serine/
arginine-rich
splicing factor 10 (SFRS10), a specific molecule functioning in alternative splicing of
lipin 1 (LPIN1) pre-mRNAs, has emerged as the central connection between
SIRT1 and lipin1 signaling. It seems a new signaling axis, SIRT1-SFRS10-LPIN1 axis, acting in the pathogenesis of AFLD exists. This article aims to further explore the interactions among the above three molecules and their influences on the development of AFLD. Impact statement ALD is a major health burden in industrialized countries as well as China. AFLD, the earliest and reversible form of ALD, can progress to
hepatitis,
fibrosis/
cirrhosis, even
hepatoma. While the mechanisms, by which
ethanol consumption leads to AFLD, are complicated and multiple, and remain incompletely understood.
SIRT1, SFRS10, and LIPIN1 had been separately reported to participate in lipid metabolism and the pathogenesis of AFLD. Noteworthy, we found the connection among them via searching articles in PubMed and we had elaborated the connection in detail in this minireview. It seems a new signaling axis, SIRT1-SFRS10-LIPIN1 axis, acting in the pathogenesis of AFLD exists. Further study aimed at SIRT1-SFRS10-LIPIN1 signaling system will possibly offer a more effective therapeutic target for AFLD.