Gut inflammation exacerbates hepatic injury in C57BL/6J mice via gut-vascular barrier dysfunction with high-fat-incorporated meat protein diets.

AIM: Meat and its derivatives provide nutrients essential for human health. However, meat consumption, along with excessive fat intake, has been associated with gut inflammation, intestinal barrier dysfunction and alterations in gut microbiota. Herein, we investigated whether and how these changes in the intestinal barrier system affect the gut liver axis and hepatic injury and eventually lead to the progression of liver syndrome such as NAFLD. METHODS: Mice were fed with high fat (60% kcal) or low fat (12% kcal) along with soybean (control), chicken and pork proteins (HFCH, HFP, LFCH, and LFP) for 12 weeks. The biomarkers for liver injury were investigated after meat protein intake along with the high fat. FINDINGS: Greater amount of fat vacuoles visible in the H&E staining increased the inflammatory cell infiltration and disorganized liver structures were observed in the HFP-fed mice. Oil Red O staining revealed that the HFP-fed and HFCH-fed mice showed more lipid droplets, confirming the increased hepatic lipid accumulation. Potential serum markers for NAFLD, ALT and AST were increased in the HF meat diet groups. Key genes responsible for hepatic inflammation and lipogenesis, such as MCP-1, IL1-ß and TNF-α were upregulated. HF meat protein diet-fed mice exhibited signs of compromised liver with increased levels of endotoxin in the liver and its binding protein in serum, upregulation of TLRs in the liver, and significant increase in TG, TC, LDL-C and HDL-C concentrations. SIGNIFICANCE: Intestinal inflammation and barrier dysfunction aggravate liver injury and fibrosis due to the intake of HF meat protein diets in mice, which may contribute to the progress of liver injury and associated complications. Gut inflammation may directly contribute to the development of NAFLD, especially of the gut vascular barricade dysfunction.

High fat diet incorporated with meat proteins changes biomarkers of lipid metabolism, antioxidant activities, and the serum metabolomic profile in Glrx1-/- mice.

Red and processed meat consumption has been associated with oxidative stress, diabetes and non-alcoholic fatty liver disease (NAFLD). This study was aimed at exploring the effects of high-fat meat protein diets on potential metabolite biomarkers in Glrx1-/- mice, a well-documented mouse model to study NAFLD. Male Glrx1-/- mice were fed a control diet with 12% energy (kcal) from fat, a high-fat diet supplemented with casein (HFC) with 60% energy (kcal) from fat, and a high-fat diet supplemented with fish (HFF) or mutton proteins (HFM) for 12 weeks. The results of biochemical and histological analyses indicated that the intake of HFM increased hepatic total cholesterol, triglycerides, serum alanine transaminase and aspartate transaminase, and macro- and micro-vesicular lipid droplet accumulation, which were accompanied by altered gene expression associated with the lipid and cholesterol metabolism. HFF diet fed Glrx1-/- mice significantly ameliorated diet-induced NAFLD biomarkers compared to HFC and HFM diets. In addition, serum metabolome profiling identified metabolites specifically associated with lipid metabolism bile acid metabolism, sphingolipid and amino acid metabolism pathways. A HFM diet increased the abundance of LysoPC(15:0), LysoPC(16:0), LysoPC(20:1), LysoPE(18:2), LysoPE(22:0), LysoPE(20:6), O-arachidonoylglycidol, 12-ketodeoxycholic acid and sphinganine that are associated with NAFLD. The KEGG metabolic pathway of identified metabolites of high fat diets showed that the differential metabolites were associated with lipid metabolism, linoleic acid metabolism, amino acid metabolism, bile acid metabolism, sphingolipid metabolism, and glutathione metabolism pathways whereas HFF diet ameliorated NAFLD by modifying these pathways. These results provide potential metabolite biomarkers for NAFLD induced by HFM diet.

Meat proteins in a high-fat diet have a substantial impact on intestinal barriers through mucus layer and tight junction protein suppression in C57BL/6J mice.

Protein diets are well known for body maintenance and weight loss. However, it remains unclear whether and how different protein sources affect the intestinal epithelial integrity through tight junctions, mucus secretions and host immunity in diet-induced obesity. To evaluate possible effects, soybean, chicken and pork proteins either with low fat (12% kcal) or high fat (60% kcal) were administered to C57BL/6J mice for 12 weeks. Muc2 expression, tight junction proteins, goblet cells, and inflammatory cytokines in the colon and serum were measured. The intake of a high-fat pork protein diet decreased the number of goblet cells and inhibited Muc2 expression in the colon, which impaired the mucus barrier. Immunohistochemistry indicated decreased crypt depth and downregulation of tight junction proteins in high-fat diet fed mice, signifying losses of epithelial barriers. In addition, a pork protein diet reduces the key zonula occludens-1 and E-cadherin proteins. A high-fat meat protein diet induces colonic inflammatory injury by upregulating several key cytokines and increasing IL-1ß, TNF-α, IL-6 and IFN-γ concentrations in serum. The intake of high-fat meat protein diets resulted in the impairment of the colon barrier through mucus suppression, downregulation of tight junctions, and gut inflammation in mice.