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Blue light exposure exacerbates Western diet-induced hepatic lipid accumulation and injury via suppression of the SIRT1-NR1D1 axis
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DOI：10.1039/D6AN00267F.png)
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Abstract
En 中文
Excessive exposure to artificial blue light has been associated with circadian disruption and metabolic disorders; however; its role in hepatic lipid metabolism under dietary stress remains poorly defined. This study investigated how blue light exposure modulates Western diet-induced nonalcoholic fatty liver disease (NAFLD) and the underlying molecular mechanisms involving the NR1D1-SIRT1 metabolic axis. Male C57BL/6J mice were fed either a control or Western diet and exposed to blue light or sham illumination for 12 weeks. Hepatic morphology was evaluated by hematoxylin-eosin and Masson’s trichrome staining; whereas macrophage infiltration and expression of NR1D1 and SIRT1 were assessed by immunohistochemistry. Untargeted LC-TOFMS-based metabolomic profiling and pathway enrichment analysis were conducted to characterize global metabolic alterations across experimental groups. The results showed blue light exposure markedly aggravated Western diet-induced hepatic steatosis; ballooning; and lobular inflammation without evidence of fibrosis. Immunohistochemical staining revealed increased F4/80 positive macrophages and downregulation of NR1D1 and SIRT1 in blue light exposed; Western diet-fed (WDBL) mice; suggesting impaired mitochondrial homeostasis. Metabolomic profiling identified 113 hepatic metabolites; revealing distinct clustering by diet and light exposure. Blue light synergistically amplified Western diet-driven accumulation of long-chain and unsaturated acylcarnitines and polyunsaturated fatty acids; indicative of incomplete β-oxidation and oxidative lipid remodeling. Pathway enrichment analysis highlighted disruptions in glycerophospholipid; sphingolipid and bile acid metabolism; accompanied by reduced antioxidant cofactors (retinol; tocopherols). In conclusion; chronic blue light exposure accelerates Western diet-induced NAFLD progression by suppressing the SIRT1-NR1D1 axis; disrupting mitochondrial lipid oxidation; and promoting redox imbalance and macrophage-mediated inflammation. These findings identify environmental blue light as a metabolic stressor that synergizes with dietary lipid overload to drive hepatic injury; offering new mechanistic insight into light-associated metabolic liver disease.
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