# Opn3 Drives Blue-Light-Induced Reduction in Lipid Droplets and Antiviral Defense

## TL;DR

Blue light, through the protein Opn3, reduces fat buildup in cells and fights viruses, offering new treatment ideas for metabolic and viral diseases.

## Contribution

This study identifies Opn3 as a key mediator of blue light's effects on lipid metabolism and antiviral defense.

## Key findings

- Blue light reduces lipid droplets and cholesterol via Opn3 and Pparα/p62 signaling.
- Blue light and Opn3 promote autophagy, aiding lipid droplet degradation.
- Blue light via Opn3 suppresses replication of multiple viruses and reduces inflammation.

## Abstract

Abnormal lipid metabolism is a key feature of many diseases. Therefore, investigating its underlying mechanisms is of great importance. Recently, blue light has shown promise as a drug-free way to influence energy metabolism, relying on the light-sensitive protein Opsin 3 (Opn3). This study aimed to investigate the effects of blue light irradiation on lipid droplet degradation in cells and its molecular mechanism, while also evaluating its potential antiviral effects. The results demonstrate that exposure to 470–480 nm blue light significantly reduced oleic-acid-induced intracellular lipid droplet accumulation and decreased triglyceride and total cholesterol levels, an effect dependent on the Opn3. It was found that blue light affects the Pparα signaling pathway through Opn3, and, at the same time, blue light and Opn3 promote autophagy mediated by p62 protein, thereby cooperatively regulating lipid droplet degradation. In Opn3 knockout cells, blue-light-induced lipid droplet degradation, nuclear accumulation of Pparα, and autophagic effects were all suppressed. Additionally, the study unexpectedly observed that blue light, via Opn3, significantly suppressed the replication of VSV, H1N1 and EMCV and alleviated virus-induced cell death and inflammatory responses. This study reveals the critical role of the blue light–Opn3-Pparα/p62 axis in regulating lipid droplet degradation in hepatocytes and identifies a novel antiviral function of Opn3-mediated blue light exposure. These findings provide a new theoretical basis and potential targets for innovative therapeutic strategies against metabolic diseases and viral infections.