Val‐Val‐Tyr‐Pro protects against non‐alcoholic steatohepatitis in mice by modulating the gut microbiota and gut‐liver axis activation

Abstract

Val‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae , coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus . Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH.

Sacha Inchi Oil Press-Cake Protein Hydrolysates Exhibit Anti-Hyperuricemic Activity via Attenuating Renal Damage and Regulating Gut Microbiota

“…Gut microbiota, as an important component of the intestine, plays an active role in UA excretion [ 9 , 47 ]. In accordance, previous studies indicated that the anti-hyperuricemic effects of some oligopeptides were mediated by the gut microbiota, such as tuna meat oligopeptides [ 40 ], Val-Val-Tyr-Pro peptide [ 48 ], and Apostichopus japonicus oligopeptide [ 49 ]. As reported, the diversity of intestinal flora in the hyperuricemia group is generally lower than that in the normal group [ 50 ].…”

Astragalus mongholicus polysaccharides ameliorate hepatic lipid accumulation and inflammation as well as modulate gut microbiota in NAFLD rats

“…45 Similar finding was also demonstrated in the mitigating effect of Val-Val-Tyr-Pro (VVYP) peptide against non-alcoholic steatohepatitis, in which the abundance of Desulfovibrionaceae was also increased. 46 These findings indicated that modulation of the gut microbiota may partly explain the beneficial effects of mAPS against NAFLD.…”

Yinzhihuang oral liquid protects against non-alcoholic steatohepatitis via modulation of the gut-liver axis in mice

“…However, the precise association between gut microbiota and NASH presently remains unclear (45). Except for the perturbation of the intestinal microbiota occurring in patients with NASH (46), the 16S rRNA sequence data showed microbiota dysbiosis in NAFLD and NASH mouse models (47)(48)(49). The current study showed that YZH modulated the composition of gut microbiota rather than increasing the variety of intestinal microbiota.…”