Dataset Information

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

ABSTRACT:

Background

Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI).

Methods

Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI.

Results

Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning.

Conclusions

These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

SUBMITTER: Naimimohasses S

PROVIDER: S-EPMC9182470 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

Naimimohasses Sara S O'Gorman Philip P Wright Ciara C Ni Fhloinn Deirdre D Holden Dean D Conlon Niall N Monaghan Ann A Kennedy Megan M Gormley John J Beddy Peter P Finn Stephen Patrick SP Lysaght Joanne J O'Sullivan Jacintha J Dunne Margaret R MR Norris Suzanne S Moore J Bernadette JB

Nutrients 20220525 11

<h4>Background</h4>Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI).<h4>Methods</h4>Mult ...[more]

PMID: 35683998

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Project description:Introduction/purposeDietary restriction (DIET) and aerobic exercise (AEX) interventions may impact energy balance differently. Our aim was to describe the effects of weight loss interventions via DIET or AEX on measures of energy balance.MethodsAdults with overweight or obesity were randomized to 12 weeks of DIET or AEX with similar calorie deficit goals. A study day was conducted before and after the intervention to assess subjective and hormonal (ghrelin, peptide-YY, glucagon-like peptide-1) appetite responses to a control meal, ad libitum energy intake (EI) at a single meal, and over three days of free-living conditions and eating behavior traits. Resting metabolic rate (RMR) was measured with indirect calorimetry and adjusted for body composition measured by dual X-ray absorptiometry. Non-exercise activity was measured using accelerometers.ResultsForty-four individuals were included (age: 37 ± 9 years, body mass index: 30.6 ± 3.1 kg/m2). Both interventions resulted in weight and fat mass loss. The DIET group lost fat-free mass, although differences between groups were not significant (DIET: -1.2 ± 1.7 kg, p<0.001; AEX: 0.4 ± 1.5 kg, p=0.186; p=0.095 interaction). There were no differences in RMR after body composition adjustment. Both interventions were associated with an increase in dietary restraint (DIET: 4.9 ± 1.2, AEX: 2.8 ± 0.7; p<0.001 in both groups). Hunger decreased with DIET (-1.4 ± 0.5, p=0.003), and disinhibition decreased with AEX (-1.5 ± 0.5, p<0.001), although these changes were not different between groups (i.e., no group × time interaction). No other differences in appetite, EI, or non-exercise physical activity were observed within or between groups.ConclusionsAEX did not result in compensatory alterations in appetite, ad libitum EI, or physical activity, despite assumed increased energy expenditure. Modest evidence also suggested that disinhibition and hunger may be differentially impacted by weight loss modality.

Project description:Background and aimsIt is unclear whether rs738409 (p.I148M) missense variant in patatin-like phospholipase domain-containing 3 rs738409 promotes fibrosis development by triggering specific fibrogenic pathways or by creating an unfavorable microenvironment by promoting steatosis, inflammation, and ultimately fibrosis. We tested the hypothesis that intermediate histologic traits, including steatosis, lobular and portal inflammation, and ballooning may determine the effect of rs738409 on liver fibrosis among individuals with biopsy-proven NAFLD.Approach and resultsCausal mediation models including multiple mediators in parallel or sequentially were performed to examine the effect of rs738409, by decomposing its total effect on fibrosis severity into direct and indirect effects, mediated by histology traits in 1153 non-Hispanic White patients. Total effect of rs738409 on fibrosis was β = 0.19 (95% CI: 0.09-0.29). The direct effect of rs738409 on fibrosis after removing mediators' effects was β = 0.09 (95% CI: 0.01-0.17) and the indirect effect of rs738409 on fibrosis through all mediators' effects were β = 0.010 (95% CI: 0.04-0.15). Among all mediators, the greatest estimated effect size was displayed by portal inflammation (β = 0.09, 95% CI: 0.05-0.12). Among different sequential combinations of histology traits, the path including lobular inflammation followed by ballooning degeneration displayed the most significant indirect effect (β = 0.023, 95% CI: 0.011-0.037). Mediation analysis in a separate group of 404 individuals with biopsy-proven NAFLD from other races and ethnicity showed similar results.ConclusionsIn NAFLD, nearly half of the total effect of the rs738409 G allele on fibrosis severity could be explained by a direct pathway, suggesting that rs738409 may promote fibrosis development by activating specific fibrogenic pathways. A large proportion of the indirect effect of rs738409 on fibrosis severity is mediated through portal inflammation.

Project description:Background and Aims: Lifestyle (exercise and dietary) modification is the mainstay of treatment for non-alcoholic fatty liver disease (NAFLD). However, there is paucity of data on effect of intensity of exercise in management of NAFLD, and we aimed to study the effect of variable intensities of exercise on NAFLD. Methods: The study was performed in the Department of Gastroenterology of the SCB Medical College, Cuttack and the Biju Patnaik State Police Academy, Bhubaneswar. The subjects were police trainees [18 in a moderate intensity exercise group (MIG) and 19 in a low intensity exercise group (LIG)] recruited for a 6-month physical training course (261.8 Kcalorie, 3.6 metabolic equivalent in MIG and 153.6 Kcalorie, 2.1 metabolic equivalent in LIG). NAFLD was diagnosed by ultrasonography, with exclusion of all secondary causes of steatosis. All participants were evaluated by anthropometry (weight, height, body mass index (BMI), waist circumference), assessed for blood pressure and biochemical parameters (blood glucose, liver function test, lipid profile, serum insulin), and subjected to transabdominal ultrasonography before and after 6 months of physical training, and the results were compared. Results: Both the groups had similar BMI, fasting plasma glucose, AST, gamma-glutamyl transpeptidase, insulin, and homeostatic model assessment-insulin resistance (known as HOMA-IR) (p>0.05). However, subjects in the LIG were older and had lower alanine transaminase, higher triglycerides and lower high-density lipoproteins than MIG subjects. There was a significant reduction in BMI (27.0±2.1 to 26.8±2.0; p=0.001), fasting blood glucose (106.7±21.6 to 85.8±19.0; p<0.001), serum triglycerides (167.5±56.7 to 124.6±63.5; p=0.017), total cholesterol (216.8±29.2 to 196.7±26.6; p=0.037), low-density lipoprotein cholesterol (134.6±21.4 to 130.5±21.9; p=0.010), serum aspartate transaminase (39.3±32.2 to 30.9±11.4; p<0.001), serum alanine transaminase (56.6±28.7 to 33.0±11.3; p<0.001) and HOMA-IR (2.63±2.66 to 1.70±2.59; p<0.001) in the MIG. However, changes in these parameters in the LIG were non-significant. Hepatic steatosis regressed in 66.7% of the NAFLD subjects in the MIG but in only 26.3% of the LIG NAFLD subjects (p=0.030). Conclusions: Moderate rather than low intensity physical activity causes significant improvement in BMI, serum triglycerides, cholesterol, serum transaminases and HOMA-IR, and regression of ultrasonographic fatty change in liver among NAFLD subjects.

Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2.MethodsMethylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used.ResultsBoth LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention.ConclusionsWe highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771).

Dataset Information

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

Background

Methods

Results

Conclusions

Publications

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

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