Exercise, Postprandial Lipids and Risk of Non-Alcoholic Fatty Liver Disease

Page, Richard

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of liver disorders from fatty accumulation to non-alcoholic steatohepatitis (NASH). The worldwide prevalence of NAFLD is estimated to be 30% and it is frequently observed in those living with obesity and Type 2 Diabetes Mellitus (T2DM). Despite this there is an apparent gap between the numbers diagnosed and the prevalence within the general population. Composite scoring panels consisting of routinely acquired anthropometric and biochemical variables provide a convenient method to identify those at risk of NAFLD and disease progression. In addition to health care settings, these panels could also be used for research purposes in population-based observational studies. The first chapter of this thesis therefore sought to estimate the prevalence of NAFLD and hepatic fibrosis in a retrospective cross-sectional cohort study of apparently healthy young to middle-aged adults using several NAFLD composite scoring panels. A second aim of the study was to examine the cross-sectional associations between selected lifestyle variables and other predictors of metabolic risk with estimates of hepatic steatosis and fibrosis using structural equation modelling (SEM).
Using the Fatty Liver Index (FLI) (Bedogni et al., 2006) the estimated prevalence of NAFLD was 34.9% within a cohort of 364 apparently healthy adults. The prevalence and severity of hepatic fibrosis varied significantly according to the composite fibrosis scoring panel selected and cut-off applied. In those participants with presumed NAFLD (FLI ≥ 60), the estimated prevalence of fibrosis was typically 20-50%; although estimates of advanced fibrosis were lower and more variable between panels. The SEM analysis identified the latent variable of metabolic syndrome (MetS) diagnosis as a predictor of liver fat (p < 0.001); and total and regional adiposity measures, as indicated by body mass index (BMI) and waist circumference (WC) as predictors of hepatic fibrosis (p < 0.001). Both BMI and WC (in conjunction with routine lipid and liver function tests [LFTs]) may be used as simple non-invasive measures to identify those individuals at a higher risk of hepatic fibrosis. These anthropometric measures were therefore used to inform the inclusion criteria for Chapter 5 and Chapter 6, respectively.
Lifestyle changes, including dietary modifications and increased physical activity/structured exercise, are advocated for the management of NAFLD. In terms of specific dietary factors, fructose consumption has been associated with poor metabolic health and acutely increases postprandial triglyceride (TG) concentrations, a risk factor for cardiometabolic disease, including NAFLD. Conversely, acute exercise is an established method to attenuate disturbances in postprandial TG and glucose metabolism. Clinical and research evaluation of postprandial lipid metabolism has largely focused on the utility of the oral fat tolerance test (OFTT) to best exemplify risk of NAFLD and atherosclerotic vascular disease. The purpose of Chapter 5 was therefore to investigate the acute ingestion of an alternative oral metabolic challenge; namely fructose included within an OFTT. This study also examined the influence of prior evening exercise on postprandial metabolism in apparently healthy men. As informed by Chapter 4, non-obese, physically active males were recruited (sedentary participants and those with clinical obesity [BMI ≥ 30 kg.m-2 or WC ≥ 94 cm] were excluded from the study). Following a screening visit, eight adult males (age [median, IQR]: 25 [2] years, BMI [mean, SD]: 25.1 [1.7] kg.m-2, WC [mean, SD]: 85.4 [4.2] cm, and self-reported physical activity > 150 minutes per week) ingested an OFTT with the addition of fructose (OFTT-Fruc; 73 g fat, 60 g fructose, 14 g protein) or sucrose (OFTT-Sucr; 73 g fat, 60 g sucrose, 14 g protein) on four separate morning visits. Volunteers rested or performed supervised prior evening exercise (40 minutes submaximal high intensity interval exercise, [HIIE]) the evening before each OFTT. OFTT-Fruc significantly increased the TG integrated area under the curve (iAUC) (p = 0.024, partial eta squared [ηp2] = 0.542) compared to OFTT-Sucr. Prior evening HIIE did not attenuate the TG response to either OFTT-Fruc or OFTT-Sucr.
The final experimental chapter of this thesis extended the methods utilised in Chapter 5 and included individuals at higher risk of MetS and NAFLD. Following a screening visit, five inactive, overweight and centrally obese adult males (age [median, IQR]: 54 [20] years, BMI [mean, SD]: 32.7 [4.2] kg.m-2, WC [mean, SD]: 113.9 [13.3] cm) and self-reported physical activity < 150 minutes per week) ingested either OFTT-Fruc or OFTT-Sucr on four separate days as outlined above. Similarly, participants either rested or performed supervised prior evening HIIE the evening before each OFTT. OFTT-Fruc significantly increased the TG total area under the curve (tAUC) (p = 0.010, ηp2 = 0.838) compared to OFTT-Sucr. There was a trend towards statistical significance and a large effect size for the lowering of the TG tAUC (by approximately 12%) following prior evening HIIE (p = 0.067, ηp2 = 0.610).
The primary outcomes of this thesis demonstrate that the likely prevalence of NAFLD in an apparently healthy cross-sectional cohort of self-selected adults attending for preventive health assessment is in accordance with previous estimates from population-based surveys. Namely, participants with presumed NAFLD (as defined by an FLI ≥ 60), were predominantly male (90.3%), older to middle-aged, clinically and abdominally obese (with significantly higher BMI, body fat content and enlarged WC). They were evidently dyslipidaemia with higher blood pressure and a higher prevalence of MetS diagnosis (up to 60%) compared to those individuals with an FLI < 10 (p < 0.001 for all above cited variables, respectively). Consistently, they were more likely to be inactive with lower cardiorespiratory fitness (predicted maximal oxygen uptake [V̇O2max]). Likewise, liver enzymes, especially gamma-glutamyl transferase (GGT), were significantly higher (p < 0.001) but typically within the routine normal reference range and participants self-reported comparable modest alcohol consumption (median [IQR]: 10 [11] units per week). The predicted prevalence of hepatic fibrosis was inconsistent from biopanel estimates ranging from 0% to 77.17% depending on the complexity of the composite panel and cut-off applied. Furthermore, BMI and WC may be utilised with routine lipids and LFTs to identify those with NAFLD at a higher risk of hepatic fibrosis. These simple measures could be easily integrated into the primary care setting to identify those requiring referral for specialist hepatic medical imaging. The risk of NAFLD and NASH/hepatic fibrosis has been strongly associated with disturbances in postprandial lipid metabolism and sub-clinical inflammatory/oxidative processes. This thesis also examined the influence of fructose included within an OFTT. The inclusion of fructose within an OFTT produced a significantly higher TG response in both apparently healthy lean physically active males and overweight/centrally obese inactive adult males. In those at risk of MetS and NAFLD, prior evening HIIE attenuated post-challenge TG responses the following morning; an effect not observed in those with lower NAFLD risk status (normolipidaemia, non-obese and more active adult males).

Citation

Page, R. Exercise, Postprandial Lipids and Risk of Non-Alcoholic Fatty Liver Disease. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4866495

• Thesis Type: Thesis
• Deposit Date: Oct 15, 2024
• Publicly Available Date: Oct 29, 2024
• Public URL: https://hull-repository.worktribe.com/output/4866495
• Additional Information: School of Sport, Exercise and Rehabilitation Sciences; University of Hull
• Award Date: Jun 18, 2024