Research Article Details
| Article ID: | A06056 |
| PMID: | 33026380 |
| Source: | Food Funct |
| Title: | Gut inflammation exacerbates hepatic injury in C57BL/6J mice via gut-vascular barrier dysfunction with high-fat-incorporated meat protein diets. |
| Abstract: | 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-β 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. |
| DOI: | 10.1039/d0fo02153a |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |