Dietary chlorogenic acid alleviates high-fat diet-induced steatotic liver disease by regulating metabolites and gut microbiota.

The high-fat diet would lead to excessive fat storage in the liver to form metabolic dysfunction-associated steatotic liver disease (MASLD), and the trend is burgeoning. The aim of the study is to investigate the effects of chlorogenic acid (CGA) on metabolites and gut microorganisms in MASLD mice induced by a high-fat diet. In comparison to the HF group, the TC (total cholesterol), TG (total triglycerides), LDL-C (low-density lipoprotein cholesterol), AST (aspartate aminotransferase) and ALT (alanine transaminase) levels were reduced after CGA supplement. CGA led to an increase in l-phenylalanine, l-tryptophan levels, and promoted fatty acid degradation. CGA increased the abundance of the Muribaculaceae, Bacteroides and Parabacteroides. Changes in these microbes were significantly associated with the liver metabolites level and lipid profile level. These data suggest important roles for CGA regulating the gut microbiota, liver and caecum content metabolites, and TG-, TC- and LDL-C lowering function.

Citrus peel ameliorates mucus barrier damage in HFD-fed mice.

Citrus peel is rich in bioactive components, especially polyphenols, which are considered to have great potential in the prevention of intestinal diseases. The intestinal mucus barrier is the first defense against the invasion of foreign substances. In this study, we aimed to explore the possibility and mechanism of citrus peel in alleviating the mucus barrier damage in high-fat-diet (HFD) mice. We found that citrus peel powder (CPP) supplementation effectively reduced body weight, fat weight, intestinal permeability, hyperlipidemia, and systemic inflammation in HFD-fed mice. In particular, CPP increased the number of goblet cells, the protein expression of Mucin-2 (Muc2), and the thickness of the mucus layer, thereby strengthening the colonic mucus barrier function. Moreover, CPP supplementation also reduced the expression of endoplasmic reticulum stress (ERS) proteins (GRP78 and CHOP) and increased the expression of T-synthase (O-glycosylation rate-limiting enzyme) and its chaperone protein (Cosmc) in the colon of HFD-fed mice, which suggested that CPP could improve the abnormal protein folding and O-glycosylation of Muc2 during processing and modification. In summary, our study indicates that CPP plays an effective role in relieving mucus barrier damage by improving the production and properties of Muc2, providing new perspectives on the development of CPP as a dietary supplement for strengthening the intestinal barrier.

Si-Wu Water Extracts Protect against Colonic Mucus Barrier Damage by Regulating Muc2 Mucin Expression in Mice Fed a High-Fat Diet.

A high-fat diet (HFD) could cause gut barrier damage. The herbs in si-wu (SW) include dang gui (Angelica sinensis (Oliv.) Diels), shu di huang (the processed root of Rehmannia glutinosa Libosch.), chuan xiong (rhizome of Ligusticum chuanxiong Hort.), and bai shao (the root of Paeonia lactiflora f. pilosella (Nakai) Kitag.). Si-wu water extracts (SWE) have been used to treat blood deficiency. Components of one herb from SW have been reported to have anti-inflammatory and anti-obesity activities. However, there have been no reports about the effects of SWE on gut barrier damage. Therefore, the aim of the study was to explore the effect of SWE on gut barrier damage. In this study, we found that SWE effectively controlled body weight, liver weight, and feed efficiency, as well as decreased the serum TC level in HFD-fed mice. Moreover, SWE and rosiglitazone (Ros, positive control) increased the colonic alkaline phosphatase (ALP) level, down-regulated serum pro-inflammatory cytokine levels, and reduced intestinal permeability. In addition, SWE increased goblet cell numbers and mucus layer thickness to strengthen the mucus barrier. After supplementation with SWE and rosiglitazone, the protein expression of CHOP and GRP78 displayed a decrease, which improved the endoplasmic reticulum (ER) stress condition. Meanwhile, the increase in Cosmc and C1GALT1 improved the O-glycosylation process for correct protein folding. These results collectively demonstrated that SWE improved the mucus barrier, focusing on Muc2 mucin expression, in a prolonged high-fat diet, and provides evidence for the potential of SWE in the treatment of intestinal disease-associated mucus barrier damage.

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD).

Gannan navel orange and Jinggang pomelo, belonging to the genus Citrus, are good sources of phenolic compounds, which are mainly concentrated in the peel. These phenolic compounds are considered promising in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). In order to maximize nutrients retention and bioactivity in the peel, pomelo peel and orange peel were processed using freeze-drying technology and mixed in the ratio (pomelo peel powder 50% and orange peel powder 50%) to make citrus peel powder (CPP). The purpose of this study was to explore new strategies and mechanisms associated with the consumption of CPP to alleviate nonalcoholic fatty liver injury, lipid metabolism disorders, and gut microbiota dysbiosis in obese mice induced by high-fat diet (HFD). The results showed that after 12 weeks of CPP administration, CPP supplementation had a strong inhibitory effect on HFD-induced weight gain, hepatic fat accumulation, dyslipidemia, and the release of pro-inflammatory cytokines. In particular, CPP modulates the composition of the intestinal flora, such as increasing the relative abundance of phylum Firmicutes, genus Faecalibaculum, genus Lactobacillus, genus Dubosiella, and genus Lachnospiraceae_NK4A136_ group and decreasing the relative abundance of phylum Bacteroidota, genus Helicobacter, and genus Bacteroides. These results suggest that CPP has a preventive effect on NAFLD, which can be related to the regulation of intestinal flora.