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. 2022 Jul;6(7):1516-1526.
doi: 10.1002/hep4.1932. Epub 2022 Mar 15.

Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD

Theresia M Schnurr  1   2 , Sophia Figueroa Katz  1   3 , Johanne M Justesen  1   2 , Jack W O'Sullivan  1 , Peter Saliba-Gustafsson  1   4 , Themistocles L Assimes  1   5 , Ivan Carcamo-Orive  1   6 , Aijaz Ahmed  7 , Euan A Ashley  1   8   9 , Torben Hansen  2 , Joshua W Knowles  1   6   10
Affiliations

Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD

Theresia M Schnurr et al. Hepatol Commun. 2022 Jul.

Abstract

Genetic predisposition and unhealthy lifestyle are risk factors for nonalcoholic fatty liver disease (NAFLD). We investigated whether the genetic risk of NAFLD is modified by physical activity, muscular fitness, and/or adiposity. In up to 242,524 UK Biobank participants without excessive alcohol intake or known liver disease, we examined cross-sectional interactions and joint associations of physical activity, muscular fitness, body mass index (BMI), and a genetic risk score (GRS) with alanine aminotransferase (ALT) levels and the proxy definition for suspected NAFLD of ALT levels > 30 U/L in women and >40 U/L in men. Genetic predisposition to NAFLD was quantified using a GRS consisting of 68 loci known to be associated with chronically elevated ALT. Physical activity was assessed using accelerometry, and muscular fitness was estimated by measuring handgrip strength. We found that increased physical activity and grip strength modestly attenuate genetic predisposition to elevation in ALT levels, whereas higher BMI markedly amplifies it (all p values < 0.001). Among those with normal weight and high level of physical activity, the odds of suspected NAFLD were 1.6-fold higher in those with high versus low genetic risk (reference group). In those with high genetic risk, the odds of suspected NAFLD were 12-fold higher in obese participants with low physical activity versus those with normal weight and high physical activity (odds ratio for NAFLD = 19.2 and 1.6, respectively, vs. reference group). Conclusion: In individuals with high genetic predisposition for NAFLD, maintaining a normal body weight and increased physical activity may reduce the risk of NAFLD.

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Conflict of interest statement

E.A.A. reports advisory board fees from Apple, DeepCell, AstraZeneca and Personalis, outside the submitted work. The other authors have nothing to report.

Figures

FIGURE 1
FIGURE 1
Plasma alanine aminotransferase (ALT) levels (in U/L) as a function of genetic risk score (GRS; number of ALT‐increasing risk alleles) stratified by levels of physical activity, grip strength, and body weight status. The lines in the panels depict regression lines, and the light shading shows the 95% confidence intervals. The ALT‐increasing effect of a higher GRS was attenuated by increasing levels of physical activity and grip strength, whereas it was amplified by increasing adiposity (all p values < 0.001). BMI, body mass index
FIGURE 2
FIGURE 2
The observed interaction effects between the GRS and physical activity, grip strength, and adiposity translated into median ALT levels. The box plots depict medians and interquartile ranges, and the whiskers extend to the fifth and 95th percentiles of ALT levels (in U/L). The NAFLD‐increasing effect of a higher GRS on ALT levels was attenuated by increasing levels of physical activity and grip strength, whereas it was amplified by increasing adiposity (all p values < 0.001). Sex‐stratified plots are shown in Figure S3
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References

    1. Brunt EM, Wong V‐S, Nobili V, Day CP, Sookoian S, Maher JJ, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1:15080. - PubMed
    1. Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta‐analysis. J Hepatol. 2019;71:793–801. - PubMed
    1. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up. Hepatology. 2015;61:1547–54. - PubMed
    1. Sookoian S, Pirola CJ. Non‐alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol. 2008;49:600–7. - PubMed
    1. Rodriguez‐Araujo G. Nonalcoholic fatty liver disease: implications for endocrinologists and cardiologists. Cardiovasc Endocrinol Metab. 2020;9:96–100. - PMC - PubMed

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