Abstract

BackgroundFatty 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.MethodsGuinea 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.ResultsWe 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.ConclusionsAscorbate ameliorates hepatic steatosis and improves insulin sensitivity through inhibiting lipogenesis and SOCS3.

Highlights

  • Metabolic syndrome has become an epidemic case with detrimental effects on public health and is thought to be an origin of many other metabolic diseases

  • Ascorbate ameliorates hepatic steatosis and insulin resistance in Guinea pigs In order to establish an ideal animal model for testing ascorbate effects, the guinea pig was chosen as the candidate, since it is a species of rodent that cannot synthesis ascorbate like human kind and is vulnerable to fat intake

  • H&E and oil red O staining results showed that the ascorbate interventions ameliorated hepatic steatosis as well as lipid droplets accumulation, which was consistent with biochemical results (Fig. 1e)

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Summary

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. 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
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