Prophylactic and therapeutic effects of different doses of vitamin C on high-fat-diet-induced non-alcoholic fatty liver disease in mice

Qingmin Zeng,Lili Zhao,Chao Meng,Xiaotong Zhao,Yonggang Liu,Ruifang Shi,Xu Han,Ting Wang,Jia Li

doi:10.1016/j.biopha.2020.110792

Abstract

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). However, the intervention dose of Vc, and the prophylactic and therapeutic effects on NAFLD are unclear. This study aimed to investigate the prophylactic and therapeutic effects of low (LVc), medium (MVc) and high (HVc) doses of Vc on NAFLD. C57BL/6 mice were randomly assigned to prophylactic groups (mice received a high-fat diet (HFD) concomitant with different doses of Vc) and therapeutic groups (HFD-induced NAFLD mice treated with different doses of Vc). Results showed that prophylactic LVc and MVc administration reduced the risk of NAFLD development in HFD-fed mice, as evidenced by significantly lowered body weight, perirenal adipose tissue mass, and steatosis, whereas prophylactic HVc administration did not prevent HFD-induced NAFLD development. Furthermore, therapeutic MVc administration significantly ameliorated HFD-induced increase in body weight, perirenal adipose tissue mass and steatosis, whereas therapeutic LVc and HVc administration did not ameliorate NAFLD symptoms. In fact, therapeutic HVc administration significantly increased body weight, perirenal adipose tissue mass, and lobular inflammation. Moreover, prophylactic LVc administration was more effective than therapeutic LVc administration as evidenced by significantly lower body weight, perirenal adipose tissue mass, steatosis, ballooned hepatocytes, and lobular inflammation in prophylactic LVc administration. The same trends were observed between prophylactic HVc administration and therapeutic HVc administration. In addition, all Vc-administered mice exhibited low blood glucose, triglycerides and homeostasis model assessment of insulin resistance values and high adiponectin levels compared to HFD-fed mice. Our study suggested that MVc was beneficial for HFD-induced NAFLD prophylaxis and therapy. LVc prevented HFD-induced NAFLD development, while HVc for NAFLD management was risky. This study offers valuable insight into the effect of various Vc doses on NAFLD management.

Highlights

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD)
Effects of different Vc doses on body weight and perirenal adipose tissue mass The Body weight and perirenal adipose tissue mass are shown in Fig. 2; both significantly increased in high-fat subgroup (HF) mice compared to control mice (P < 0.05)
P-Low-dose Vc subgroup (LVc) mice showed significantly decreased body weight and perirenal adipose tissue mass compared to P-HF mice (P < 0.05), while T-LVc mice tended to show increased body weight and perirenal adipose tissue mass compared to to high-fat (T-HF) mice

Summary

Introduction

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome associated with obesity, insulin resistance (IR), type 2 diabetes mellitus, and dyslipidemia[1, 2]. Adiponectin is an adipocyte-derived secretory protein that acts by binding and activating two different receptor isoforms (AdipoRI and AdipoRII) and exerts beneficial systemic metabolic effects by acting on adipogenesis, atherosclerosis, insulin sensitivity, and inflammation[5]. It is strongly associated with the risk of metabolic syndrome as well as the development and progression of NAFLD[6,7,8]

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