scholarly journals Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zunji Shi ◽  
Hehua Lei ◽  
Gui Chen ◽  
Peihong Yuan ◽  
Zheng Cao ◽  
...  

ABSTRACT Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.

2019 ◽  
Vol 49 (5) ◽  
pp. 903-910 ◽  
Author(s):  
Mehrnaz Nikkhah-Bodaghi ◽  
Matin Ghanavati ◽  
Azita Hekmatdoost

PurposePolyphenols are plant-derived bioactive compounds with some known hepato-protective effects. The purpose of this study is to evaluate the association between polyphenol consumption and risk of nonalcoholic fatty liver disease (NAFLD) and its related conditions such as impaired lipid profile and elevated hepatic enzymes.Design/methodology/approachA total of 196 NAFLD patients and 803 controls were enrolled in this case-control study. Biochemical and anthropometric measurements as well as polyphenol consumption during the previous year were assessed.FindingsIn unadjusted model, participants who consumed the third and fourth quartiles of polyphenols intake were less likely to have NAFLD in comparison to those who consumed the first quartile [odds ratio, OR: 0.48; 95 per cent confidence interval, CI: (0.30-0.77) and OR: 0.62; 95 per cent CI: (0.40-0.96), respectively]. In separate analysis of genders, this effect was seen only in male participants [OR: 0.29; 95 per cent CI: (0.14-0.58) and OR: 0.21; 95 per cent CI (0.10-0.42), respectively], and the association remained significant after adjustment for energy, body mass index, age and smoking.Originality/valueHigher total polyphenol intake is associated with a decreased risk of NAFLD. Prospective studies are needed to confirm these results.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Alifia Mukti Fajrani ◽  
Mohamad Sulchan ◽  
Siti Fatimah Muis ◽  
Hery Djagat Purnomo ◽  
Kis Djamiatun ◽  
...  

Purpose This paper aims to determine the effect of black garlic (BG) on visceral fat, oxidative stress and insulin resistance (IR) compared with metformin and vitamin E in nonalcoholic fatty liver disease (NAFLD) rats. Design/methodology/approach A randomized post-test only design with control group was used in this study. Rats were given high-fat fructose diet enriched with 1.25% cholesterol and 0.5% cholic acid for eight weeks to induce NALFD condition. The administration of BG dose of 450 mg/200 gBW, 900 mg/200 gBW and 1350 mg/200 gBW with a comparative control of 45 mg/200 gBW of metformin and vitamin E of 9 IU/200 gBW were given for four weeks via oral gavage to reduce visceral fat, oxidative stress and improve IR. Statistical analyses were performed to examine differences between groups with one-way analysis of variance and nonparametrics test. Findings Rats given with three different doses of BG for four weeks did not reduce body weight from 244 ± 4.4 to 284 ± 4.6 g, 242 ± 2.5 to 272 ± 3.1 g and 240 ± 2.4 to 270 ± 3.6 g, respectively, but significantly reduced visceral fat (p = 0.001) on BG groups with 3.7 ± 1.3, 2.7 ± 0.7 and 1.8 ± 0.6 g, respectively. BG improved oxidative stress (p = 0.001) with malondialdehyde level 5.1 ± 0.2, 3.0 ± 0.06 and 2.3 ± 0.06 ng/mL, respectively, but did not better than vitamin E group 1 ± 0.03 ng/mL. Significant (p = 0.001) improvement on insulin resistance with homeostatic model assessment IR in BG groups were 5.3 ± 0.1, 4.4 ± 0.1 and 4 ± 0.1, respectively, but not as good as metformin group 3.7 ± 0.1. Research limitations/implications Based on the experiment, there are several limitations including small sample size, performed on animal models in a relatively short time, did not examine organosulfurs compound (OSC) content of BG specifically and OSC affects metabolism in NAFLD remains unclear and will require further investigation. Practical implications BG is a functional food made from heated fresh garlic owing to the Maillard reaction and the organosulfur compounds as antioxidants. The higher the dose of BG, the greater the improvement in visceral fat, oxidative stress and IR in model NAFLD rats. Social implications NAFLD is a liver disorder caused by excessive fat and energy intake, the treatment strategies among others through diet modification. Originality/value In model NAFLD rats, BG administration improved NALFD markers but did not better rather than the metformin and vitamin E result.


2019 ◽  
Vol 49 (3) ◽  
pp. 359-367 ◽  
Author(s):  
Hadi Emamat ◽  
Hossein Farhadnejad ◽  
Hossein Poustchi ◽  
Azita Hekmatdoost

Purpose The purpose of this paper is to assess the association between galactose intake and risk of nonalcoholic fatty liver disease (NAFLD). Design/methodology/approach In total, 196 newly diagnosed patients with NAFLD and 803 controls were recruited from a referral hepatology clinic. Dietary intakes were assessed using a validated and reliable food frequency questionnaire. Dietary intakes of galactose were compared between cases and controls. Findings Median (interquartile range) of dietary galactose intake was 2.24 (1.36-3.53) g/day for all subjects. In age and sex adjusted-model, subjects in the highest tertile of galactose intake had more than three times higher risk of NAFLD compared with those in the lowest tertile (odds ratio [OR]: 3.05; 95 per cent confidence interval [CI]: 2.02-4.54), (p-value < 0.001). Additionally controlling for body mass index (BMI), physical activity, energy intake and dietary lactose intake, the direct association between galactose intake and NAFLD remained significant (OR: 2.77; 95 per cent CI: 1.55-4.95), (p-value < 0.001). Originality/value This study was the first one to assess the association between galactose intake and risk of NAFLD.


2019 ◽  
Vol 49 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Angelica Carreira dos Santos ◽  
Daniel Araki Ribeiro ◽  
Jessica Almeida da Cruz Ferreira ◽  
Odair Aguiar ◽  
Dan Linetzky Waitzberg ◽  
...  

Purpose The purpose of this study is to evaluate the effects of prebiotic, probiotic and synbiotic supplementation on liver histopathology and TLR-4, NFκB and TNF-α gene expression involved in the inflammatory cascade and pathogenesis of experimental nonalcoholic fatty liver disease (NAFLD). Design/methodology/approach Wistar male adult rats (n = 40) were submitted to hypercholesterolemic conditions (60 days). On Day 30 of hypercholesterolemic conditions, rats were subdivided in five groups: negative control (NC), positive control (PC), prebiotic (PRE), probiotic (PRO) and synbiotic (SYN). All rats were sacrificed on Day 60. Liver tissue was used to verify histopathological changes and gene expression. Gene expression of TLR-4, TNF-α and NFκB was evaluated in liver tissue using RT-qPCR. Findings Histopathological analysis: PC showed more changes than NC, and PRE and SYN showed fewer alterations than PC. Gene expression analysis: PRE showed higher TLR-4, and NFκB and TNF-α compared to PC. Also, PRE showed higher TLR-4 when compared to PRO and SYN. SYN group revealed higher TLR-4 and NFκB expressions compared to PC. PRO group also showed higher NFκB expression compared to PC. Originality/value NAFLD is a significant health concern, and it found that prebiotic, probiotic and synbiotic supplementation could have positive effects as a nonpharmacological approach to control this disease.


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