AUTHOR=Liu Jiaqi , Guo Chao , Wang Yuqin , Su Min , Huang Wenjun , Lai Keng Po TITLE=Preclinical insights into fucoidan as a nutraceutical compound against perfluorooctanoic acid-associated obesity via targeting endoplasmic reticulum stress JOURNAL=Frontiers in Nutrition VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.950130 DOI=10.3389/fnut.2022.950130 ISSN=2296-861X ABSTRACT=

Obesity is a growing global health problem; it has been forecasted that over half of the global population will be obese by 2030. Obesity is complicated with many diseases, such as diabetes and cardiovascular diseases, leading to an economic impact on society. Other than diet, exposure to environmental pollutants is considered a risk factor for obesity. Exposure to perfluorooctanoic acid (PFOA) was found to impair hepatic lipid metabolism, resulting in obesity. In this study, we applied network pharmacology and systematic bioinformatics analysis, such as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, together with molecular docking, to investigate the targets of fucoidan for treating PFOA-associated obesity through the regulation of endoplasmic reticulum stress (ERS). Our results identified ten targets of fucoidan, such as glucosylceramidase beta (GBA), glutathione-disulfide reductase (GSR), melanocortin 4 receptor (MC4R), matrix metallopeptidase (MMP)2, MMP9, nuclear factor kappa B subunit 1 (NFKB1), RELA Proto-Oncogene, NF-KB Subunit (RELA), nuclear receptor subfamily 1 group I member 2 (NR1I2), proliferation-activated receptor delta (PPARD), and cellular retinoic acid binding protein 2 (CRABP2). GO and KEGG enrichment analyses highlighted their involvement in the pathogenesis of obesity, such as lipid and fat metabolisms. More importantly, the gene cluster is responsible for obesity-associated diseases and disorders, such as insulin resistance (IR), non-alcoholic fatty liver disease, and diabetic cardiomyopathy, via the control of signaling pathways. The findings of this report provide evidence that fucoidan is a potential nutraceutical product against PFOA-associated obesity through the regulation of ERS.