Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B

Abstract

Inhibition of lipid accumulation is the key step to prevent nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis. We aimed to study the effect of low-molecular-weight citrus pectin (LCP) against lipid accumulation and the underlying mechanism. Oleic acid (OA)-induced lipid deposition in HepG2 cells was applied to mimic in vitro model of lipid accumulation. Oil Red O (ORO) stain result showed lipid accumulation was significantly reduced, and levels of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase-1 (CPT-1), involved in triacylglycerol catabolism and fatty acid β-oxidation, detected by RT-qPCR were increased after OA-stimulated HepG2 cells treated with LCP. RNA sequencing analysis identified 740 differentially expressed genes (DEGs) in OA-stimulated HepG2 cells treated with the LCP group (OA+LCP group), and bioinformatics analysis indicated that some DEGs were enriched in lipid metabolism-related processes and pathways. The expression of the top 8 known DEGs in the OA+LCP group was then verified by RT-qPCR, which showed that fold change (abs) of METTL7B was the highest among the 8 candidates. In addition, overexpression of METTL7B in HepG2 cells significantly inhibited the lipid accumulation and enhanced levels of ATGL and CPT-1. In conclusion, LCP inhibited lipid accumulation through the upregulation of METTL7B, and further enhancement of ATGL and CPT-1 levels. LCP is expected to develop as a promising agent to ameliorate fat accumulation in NAFL.

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Funding

This work was supported by the Natural Science Research Project of Shanghai Minhang Science and Technology Committee (2018MHZ074, 2019MHZ069) and Special Construction Project of Integrated Traditional Chinese and Western Medicine in Shanghai General Hospital (ZHYY-ZXYJHZX-201622).

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Correspondence to Yinghua Yuan.

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Fig. S1

Top 30 KEGG pathway enrichment. The size of circle indicates the number of DEGs; the color indicates the value of P. DEGs, differentially expressed genes. (JPG 351 kb)

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Yang, X., Yuan, Y. & Xie, D. Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B. Appl Biochem Biotechnol (2021). https://doi.org/10.1007/s12010-021-03486-z

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Keywords

  • Low molecular pectin
  • Lipid accumulation
  • METTL7B
  • ATGL
  • CPT-1