Ascorbate protects liver from metabolic disorder through inhibition of lipogenesis and suppressor of cytokine signaling 3 (SOCS3)

Yingying Xu, Yuhang Wu, Yue Xiong, Jiawang Tao, Tingcai Pan, Shenglin Tan, Ge Gao, Yan Chen, Nasir Abbas, Anteneh Getachew, Yuanqi Zhuang, Kai You, Fan Yang, Yin Xiong Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: Fatty liver is a reversible status, but also an origin stage to develop to other metabolic syndromes, such as diabetes and heart disease that threatens public health worldwide. Ascorbate deficiency is reported to be correlated with increasing risks for metabolic syndromes, but whether ascorbate has a therapeutic effect is unknown. Here, we investigated if ascorbate treatment alone could work on protecting from the development of steatosis and mechanisms beyond. Methods: Guinea pigs were fed with a chow diet or a high palm oil diet (HPD) respectively. HPD induced animals were administered different concentrations of ascorbate in different time intervals through water. Besides, hepatocyte-like cells derived from human embryonic stem cells and HepG2 cells were treated with palmitic acid (PA) to induce lipid accumulation for molecular mechanism study. Results: We find that ascorbate rescues HPD and PA induced steatosis and insulin tolerance in vivo and in vitro. We demonstrate that ascorbate changes cellular lipid profiles via inhibits lipogenesis, and inhibits the expression of SOCS3 via STAT3, thus enhances insulin signal transduction. Overexpression of SOCS3 abolishes the ascorbate rescue effects on insulin signal and lipid accumulation in hepatic cells. Conclusions: Ascorbate ameliorates hepatic steatosis and improves insulin sensitivity through inhibiting lipogenesis and SOCS3.

Original languageEnglish
Article number17
JournalNutrition and Metabolism
Volume17
Issue number1
DOIs
Publication statusPublished - 4 Mar 2020
Externally publishedYes

Keywords

  • Guinea pig
  • Insulin signaling
  • Lipidomics
  • Lipogenesis
  • STAT3

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Xu, Y., Wu, Y., Xiong, Y., Tao, J., Pan, T., Tan, S., Gao, G., Chen, Y., Abbas, N., Getachew, A., Zhuang, Y., You, K., Yang, F., & Li, Y. X. (2020). Ascorbate protects liver from metabolic disorder through inhibition of lipogenesis and suppressor of cytokine signaling 3 (SOCS3). Nutrition and Metabolism, 17(1), Article 17. https://doi.org/10.1186/s12986-020-0431-y