A digestive system microphysiological platform for assessment of internal-exposure risks and metabolic disease mechanisms induced by multi-size nano-plastics

Xinran Li; Yueyi Li; Bo Liu; Guodong Sui; Sixiu Liu; Guanling Song

doi:10.1016/j.jhazmat.2024.136865

A digestive system microphysiological platform for assessment of internal-exposure risks and metabolic disease mechanisms induced by multi-size nano-plastics

J Hazard Mater. 2024 Dec 12:485:136865. doi: 10.1016/j.jhazmat.2024.136865. Online ahead of print.

Authors

Xinran Li¹, Yueyi Li², Bo Liu², Guodong Sui², Sixiu Liu³, Guanling Song⁴

Affiliations

¹ Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 2005 Songhu Road, Shanghai 200438, China; Life Science Innovation Research Laboratory, Shanghai Yichuan High School, 101 Huayin Road, Shanghai 200065, China.
² Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
³ Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 2005 Songhu Road, Shanghai 200438, China. Electronic address: liusixiu@fudan.edu.cn.
⁴ Department of Preventive Medicine/the Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, School of Medicine, Shihezi University, Shihezi, Xinjiang 832000, China. Electronic address: sglhit.student@sina.com.

PMID: 39700947
DOI: 10.1016/j.jhazmat.2024.136865

Abstract

Nano-plastics (NPs) are emerging hazardous environmental contaminants that pose health risks with size-dependent toxic effects and are potential risk factors for hepatocellular carcinoma (HCC) and lipid metabolism disorders including non-alcoholic fatty liver disease (NAFLD). However, their underlying molecular mechanisms remain unclear. To shed more light on the causes of these risks, we developed a digestive system microphysiological platform (DS-MPP) for simulating dynamic internal-exposure of multi-size NPs in the gastrointestinal tract and liver. Multi-omics analysis based on DS-MPP revealed hepatic cells are more sensitive to 72 μg/day NPs than gastrointestinal mucosa cells. Specifically, 50 nm NPs disrupt phospholipid metabolism, promote diacylglycerol (DG) accumulation, convert more DG to phosphatidic acid (PA) than triacylglycerol (TG), thus facilitating endocytic vesicles production. Meanwhile, it can active tumorigenesis related pathway mTOR, inducing HCC marked by CAB39. Moreover, 500 nm NPs promote NAFLD by inducing insulin resistance pathways and decreasing PLD1 expression. Our results demonstrate the mechanism of disease and metabolic disorders induced by NPs vary depending on particle size. DS-MPP is a reliable platform for evaluating risk of dynamic NPs exposure and elucidating mechanisms of related metabolic diseases. This platform provides a promising method for health risk assessment caused by environmental pollutants.

Keywords: Digestive system; Health risk; Liver metabolic disease; Microphysiological platform; Nano-plastics.