scholarly journals Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Na Wu ◽  
Fan Yuan ◽  
Siran Yue ◽  
Fengyan Jiang ◽  
Decheng Ren ◽  
...  

Abstract Background Nonalcoholic 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. Methods Methylation 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. Results Both 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. Conclusions We 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. Trialregistration International Standard Randomized Controlled Trial Number Register (ISRCTN42622771)

2004 ◽  
Vol 107 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Matthew J. SHARMAN ◽  
Jeff S. VOLEK

In recent years, it has become apparent that low-grade vascular inflammation plays a key role in all stages of the pathogenesis of atherosclerosis. Weight loss has been shown to improve blood inflammatory markers; however, it is unknown if weight-loss diets varying in macronutrient composition differentially affect inflammatory responses. The primary purpose of the present study was to compare a very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory biomarkers in overweight men. In a randomized cross-over design, 15 overweight men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight-loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10% energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low-fat and the very-low-carbohydrate diets resulted in significant decreases in absolute concentrations of hsTNF-α (high-sensitivity tumour necrosis factor-α), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C-reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1). There was no significant change in absolute sP-selectin (soluble P-selectin) concentrations after either diet. Normalized inflammatory values represented as the delta change per 1 kg reduction in body mass showed a significant difference between the two diets only for sP-selectin (P<0.05). In summary, energy-restricted low-fat and very-low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that, in the short-term, weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Tian Hu ◽  
Kristi Reynolds ◽  
Lu Yao ◽  
Calynn Bunol ◽  
Yanxi Liu ◽  
...  

The long-term effects of low-carbohydrate diets versus low-fat diets on endothelial dysfunction and insulin resistance are unclear. A total of 148 study participants with a body mass index of 30 - 45 kg/m2 (Mean: 35.4 kg/m2) who were free of diabetes, cardiovascular diseases and kidney disease were recruited. The participants were randomly assigned to either a low-carbohydrate diet (<40 g/day; N=75) or a low fat (<30% energy from fat, <10% from saturated fat; N=73) diet. Two 24-hour dietary recalls were conducted at each clinic visit (0, 3, 6 and 12 months of intervention). Participants met with a study dietitian weekly for the first month followed by group settings bi-weekly for 5 months and monthly for the last 6 months. Each group was provided the same behavioral curriculum related to diet emphasizing portion control and eating habits. Biomarkers for endothelial function and insulin resistance included E-selectin, Intercellular Adhesion Molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), Insulin-like growth Factor-1 (IGF-1), serum insulin, and glucose. Mixed-effect regression models including group, time and their interaction were used to analyze the data. Of the study participants, 60 in the low-fat group (81.1%) and 59 in the low-carbohydrate group (79.7%) completed the entire intervention. The mean age was 46.8 years, 88.5% were women and 55.1% were African-Americans. The low-carbohydrate group lost approximately 3.5 kg more body weight than did the low-fat group (P= 0.002) on average. Compared to the low-fat diet, the low-carbohydrate diet resulted in greater reductions in E-selectin (net change: -4.5, -4.3, and -3.8 ng/mL at 3, 6, and 12 months, respectively; overall P= 0.002) and ICAM-1 (net change: -7.3, -10.4, and -16.8 ng/mL at 3, 6, and 12 months, respectively; overall P= 0.06). There was no significant change in any other markers. Our findings suggest that the low-carbohydrate is at least as effective as the low-fat diet at improving endothelial dysfunction and insulin resistance.


2010 ◽  
Vol 170 (2) ◽  
pp. 136 ◽  
Author(s):  
William S. Yancy ◽  
Eric C. Westman ◽  
Jennifer R. McDuffie ◽  
Steven C. Grambow ◽  
Amy S. Jeffreys ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. 1239-1242 ◽  
Author(s):  
P A Essah ◽  
J R Levy ◽  
S N Sistrun ◽  
S M Kelly ◽  
J E Nestler

2017 ◽  
Vol 59 (2) ◽  
pp. 34
Author(s):  
Adil Razak ◽  
Abdul Aziez Isaacs

Background: Diabetes is a common non-communicable disease and complications are resulting in increased disability, reduced life expectancy and enormous health costs for virtually every society. Medical Nutrition Therapy is important for the prevention, treatment, and self-management of diabetes, and the prevention or delay in onset of diabetes-related complications. The current nutritional guidelines for diabetes state that carbohydrates should comprise 45–60% of the total nutritional intake and that lowcarbohydrate or high-protein diets offer no long-term success over healthy eating plans. Recent studies suggest that there may be merit in using low-carbohydrate diets in diabetic patients for weight reduction and improved cardiovascular markers. This study aimed to implement and evaluate a pilot programme for weight loss in diabetes mellitus type 2 patients by comparing a low-carbohydrate diet with the conventional low-fat diet. Methods: The study design was that of a two-group parallel design, with one group following a low-fat diet and the other a low-carbohydrate diet. Diabetic patients attending the Mitchell’s Plain Community Health Centre in Cape Town were recruited, with 10 participants in each group. Both groups received similar advice on exercise and behaviour change. Changes in weight, waist circumference, blood pressure and blood parameters (creatinine, lipids and HbA1c) were recorded at baseline and again after 12 weeks. Results: There were reductions in weight (1.85 kg vs. 0.1 kg gain) and HbA1c (1.72 vs. 0.32) in the low-carbohydrate diet group when compared with the low-fat diet group. No significant change was seen in other parameters including BP, total cholesterol and serum creatinine for either group. Conclusion: Low-carbohydrate diets may be effective in promoting weight loss and improving glucose control in diabetic patients. Implementation of this programme would require a paradigm shift for staff and further studies to assess its acceptability for patients. (Full text of the research articles are available online at www.medpharm.tandfonline.com/ojfp) S Afr Fam Pract 2017; DOI: 10.1080/20786190.2017.1329490


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