Abstract
A perinatal high-salt (HS) diet was reported to elevate plasma triglycerides. This study aimed to investigate the hypothesis that a perinatal HS diet predisposed offspring to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of abnormal lipid metabolism, and the possible mechanism. Female C57BL/6 mice were fed a control diet (0.5% NaCl) or HS diet (4% NaCl) during pregnancy and lactation and their offspring were sacrificed at weaning. The perinatal HS diet induced greater variation in fecal microbial beta-diversity (β-diversity) and increased bacteria abundance of Proteobacteria and Bacteroides. The gut microbiota dysbiosis promoted bile acid homeostasis disbalance, characterized by the accumulation of lithocholic acid (LCA) and deoxycholic acid (DCA) in feces. These alterations disturbed gut barrier by increasing the expression of tight junction protein (Tjp) and occludin (Ocln), and increased systemic lipopolysaccharide (LPS) levels and hepatic inflammatory cytokine secretion (TNF-α and IL-6) in the liver. The perinatal HS diet also inhibited hepatic expression of hepatic FXR signaling (CYP7A1 and FXR), thus triggering increased hepatic expression of pro-inflammatory cytokines (TNF-α and IL-6) and hepatic lipid metabolism-associated genes (SREBP-1c, FAS, ACC), leading to unique characteristics of NAFLD. In conclusion, a perinatal HS diet induced NAFLD in weanling mice offspring; the possible mechanism was related to increased bacteria abundance of Proteobacteria and Bacteroides, increased levels of LCA and DCA in feces, and increased expressions of hepatic FXR signaling.
Highlights
Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in children and adolescents globally in recent years [1]
We examined gut microbiota, bile acid metabolism, and hepatic farnesoid X receptor (FXR) signaling in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in mice offspring
Levels (Figure 1D); levels of plasma TG, hepatic TG, and total cholesterol (TC) were increased in the offspring with perinatal HS diet (Figure 1C,E,F)
Summary
Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in children and adolescents globally in recent years [1]. NAFLD in children is a major risk factor for the development of cirrhosis and hepatocellular carcinoma in adult [2,3], and it is an early predictor of hypertension and type 2 diabetes [4,5]. Emerging evidence from human and animal studies has revealed that a high-salt (HS) diet in adulthood is a major risk factor for hypertension [9] and cardiovascular disease [10], and exerts effects on hypertriglyceridemia [11], oxidative stress, and inflammation [12], which are well-known pathological features of the development of NAFLD [13,14]. A previous epidemiological study in adults showed that HS diet was associated with increased frequencies of NAFLD [15].
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