Sirtuin 1 (
SIRT1) is a
protein deacetylase with important cellular functions, as it regulates numerous processes, including the circadian rhythm in peripheral tissues. Efforts are ongoing to reveal how
Sirt1 can be used to treat diseases, such as
alcoholic liver disease (ALD),
Alzheimer's disease, and
liver fibrosis. We have recently shown that noninvasive exposure to 40-Hz light flicker activates hypothalamic
SIRT1 gene expression, thereby regulating the central circadian clock. This study investigated the effects of 40-Hz light flicker in a mouse model of ALD.
RNA sequencing (
RNA-seq) analysis was performed to explore the potential pathways affected by 40-Hz light flicker. We found that 40-Hz light flicker significantly decreased the acute
ethanol-induced increases in serum
alanine aminotransferase (ALT) and serum
triglyceride (TG) levels and reduced fat-droplet accumulation in mouse livers. Additionally, 40-Hz light flicker significantly suppressed
ethanol-induced increases in
sterol regulatory element binding protein 1 (SREBP-1) and
fatty acid synthase (Fasn) levels. Furthermore, the
ethanol induced significant decreases in both
Sirt1 levels and phosphorylation of
adenosine monophosphate-activated
protein kinase subunit (AMPKα), compared with those in the control group. Strikingly, pretreatment with 40-Hz light flicker ameliorated such
ethanol-induced decreases in
SIRT1 levels and AMPKα phosphorylation. In addition,
ethanol-induced increases in levels of brain and muscle arnt-like protein-1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), and period 2 (PER2) were reversed by 40-Hz light flicker.
RNA-seq analysis revealed significant differences in expression of genes related to the AMPK signalling. Moreover,
ethanol consumption altered
mRNA levels of
Sirt1 and circadian genes in the suprachiasmatic nucleus (SCN), indicating that
ethanol influenced central pacemaker genes; however, 40-Hz light flicker reversed these
ethanol-induced changes. Taken together, our findings demonstrate that 40-Hz light flicker rapidly influence the SCN and exhibits inhibitory properties on hepatic lipogenesis, indicating that 40-Hz light flicker has therapeutic potential for preventing alcoholic
liver steatosis.