Chronic UVB exposure induces hepatic injury in mice: Mechanistic insights from integrated multi-omics.

ABSTRACT

Chronic UVB exposure poses a significant threat to both skin and visceral health. In recent years, the adverse role of chronic UVB exposure in liver health has been suggested but not fully elucidated. This study aims to comprehensively investigate the effects of chronic UVB exposure on liver health in male SKH-1 hairless mice and clarify potential mechanisms through multi-omics approaches. The findings suggested that 10-week chronic skin exposure to UVB not only triggers hepatic inflammation and oxidative stress but also, more importantly, results in lipid metabolism abnormalities in the liver. Hepatic transcriptomic analysis revealed significant alterations in various signaling pathways and physiological processes associated with inflammation, oxidative stress, and lipid metabolism. Further lipidomic analysis illustrated significant changes in the metabolism of glycerolipids, sphingolipids, and glycerophospholipids in the liver following chronic UVB exposure. The 16S rRNA sequencing analysis indicated that chronic UVB exposure disrupts the structure and function of the microbiota. In search of potential mechanisms used by the microbiome to regulate the hepatic disease morphology, we filtered mouse fecal supernatants and cultured the supernatants with HepG2 cells. Fecal supernatant from UVB-exposed mice induced increased secretion of the inflammatory cytokine IL-8, accumulation of MDA, reduced SOD activity, and decreased lipid content in normal hepatic cells. In summary, skin chronic exposure to UVB induces multiple liver injuries and gut microbiota dysbiosis in mice and gut microbiota metabolites may be one of the contributing factors to hepatic injury caused by chronic UVB exposure. These discoveries deepen the comprehension of the health risks associated with chronic UVB exposure.