Abstract
Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH). Non-caloric sweeteners (NCS) are food additives providing sweetness without calories and are considered safe and/or not metabolized by the liver. The potential role of newer NCS in the regulation of NASH, however, remain unknown. Our study aimed to determine the impact of newer NCS including Rebaudioside A and sucralose on NASH using high fat diet induced obesity mouse model by substituting fructose and sucrose with NCS in the drinking water. We characterized the phenotype of NCS- treated obesity and investigated the alterations of hepatic function and underlying mechanisms. We found that NCS have no impact on weight gain and energy balance in high fat diet induced obesity. However, in comparison to fructose and sucrose, Rebaudioside A significantly improved liver enzymes, hepatic steatosis and hepatic fibrosis. Additionally, Rebaudioside A improved endoplasmic reticulum (ER) stress related gene expressions, fasting glucose levels, insulin sensitivity and restored pancreatic islet cell mass, neuronal innervation and microbiome composition. We concluded that Rebaudioside A significantly ameliorated murine NASH, while the underlying mechanisms requires further investigation.
Highlights
Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH)
Compared to CH group (33.8 g ± 0.4), we observed all four groups fed on high fat diet have gained body weight significantly (p < 0.0001), we observed no significant difference in body weight gain among the high fat diet fed groups at 15 weeks of the study (p > 0.05) (HF group: 47.0 g ± 1.2; HFHC group: 48.3 g ± 1.3; HF + RE group: 46.8 g ± 1.3; HF + SU group: 48.2 g ± 1.0), indicating Non-caloric sweeteners (NCS) has no impact on weight gain while mice have access to a high fat diet (Fig. 1A)
We report data that Rebaudioside A usage is associated with improved glucose tolerance, less liver fibrosis and inflammation mediated via decreased endoplasmic reticulum (ER) stress
Summary
Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH). Recent literature has reported that Rebaudioside A may play a role in glucose metabolism and has even been reported to improve post-prandial glucose-insulin index[11], and its consumption may result in weight loss in mice fed a high fat diet[12]. These observations suggest a potential role for Rebaudioside A on glucose metabolism in general, and on liver function and NASH in particular. We performed experiments to further understand the role of NCS in metabolic outcomes[20,21] with a focus to understand the effects of NCS on glucose metabolism, liver function and changes in the microbiome
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