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Randomized Controlled Trial
. 2023 Mar 20;15(6):1481.
doi: 10.3390/nu15061481.

Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis

Jonathan G Stine  1   2   3   4 , Jaclyn E Welles  5 , Shelley Keating  6 , Zeba Hussaini  1 , Christopher Soriano  1 , J Wes Heinle  1 , Nathaniel Geyer  2 , Vernon M Chinchilli  2 , Rohit Loomba  7   8 , Scot R Kimball  5
Affiliations
Randomized Controlled Trial

Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis

Jonathan G Stine et al. Nutrients. .

Abstract

Background and aims: Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. However, mechanisms underpinning the improvements in NAFLD seen with exercise are unclear. Exercise improved liver fat and serum biomarkers of liver fibrosis in the NASHFit trial. We investigated exercise's mechanism of benefit by conducting a post hoc analysis of these data to determine the relationship between serum fibroblast growth factor (FGF) 21, which is implicated in NAFLD development, and exercise.

Methods: In the 20 wk NASHFit trial, patients with nonalcoholic steatohepatitis (NASH) were randomized to receive moderate-intensity aerobic exercise training or standard clinical care. Mediterranean-informed dietary counseling was provided to each group. Change in serum FGF21 was measured after an overnight fast.

Results: There was a significant improvement in serum FGF21 with exercise training compared to standard clinical care (p = 0.037) with serum FGF21 reducing by 22% (-243.4 +/-349 ng/mL) with exercise vs. a 34% increase (+88.4 ng/mL +/-350.3 ng/mL) with standard clinical care. There was a large inverse association between change in serum FGF21 and change in cardiorespiratory fitness (VO2peak) (r = -0.62, 95% CI -0.88 to -0.05, p = 0.031), and on multivariable analysis, change in VO2peak remained independently associated with change in FGF21 (β = -44.5, 95% CI -83.8 to -5.11, p = 0.031).

Conclusions: Serum FGF21 is markedly decreased in response to aerobic exercise training, offering a novel mechanism to explain the observed reduction in liver fat and improvement in serum biomarkers of liver fibrosis in patients with NASH who do exercise.

Keywords: biomarker; cardiorespiratory fitness; fatty liver; nonalcoholic fatty liver disease; physical activity.

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Conflict of interest statement

J.G.S. receives or has received research support from AstraZeneca, Galectin, Noom, Inc., Novo Nordisk, and Zydus. RL serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myer Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen Inc., Merck, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also the co-founder of Liponexus, Inc. All other authors have no relevant conflicts of interest to report.

Figures

Figure 1
Figure 1
Change in serum FGF21 comparing exercise training to standard clinical care. Serum FGF21 was reduced by 22% (−243 ng/mL) following exercise training, whereas standard clinical care patients had an increase of 34% (+88 ng/mL).
Figure 2
Figure 2
Correlation between change in serum FGF21 and VO2peak. Serum FGF21 reduction was significantly correlated with VO2peak gain (r = −0.62, 95% CI −0.88 to −0.05, p = 0.031). On multivariable analysis, VO2peak improvement remained independently associated with FGF21 decrease (β = −44.5, 95% CI −83.8 to −5.11, p = 0.031).
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References

    1. Younossi Z.M. Non-alcoholic fatty liver disease—A global public health perspective. J. Hepatol. 2019;70:531–544. doi: 10.1016/j.jhep.2018.10.033. - DOI - PubMed
    1. Simon T.G., Roelstraete B., Khalili H., Hagström H., Ludvigsson J.F. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: Results from a nationwide cohort. Gut. 2021;70:1375–1382. doi: 10.1136/gutjnl-2020-322786. - DOI - PMC - PubMed
    1. Schneider C.V., Zandvakili I., Thaiss C.A., Schneider K.M. Physical activity is associated with reduced risk of liver disease in the prospective UK Biobank cohort. JHEP Rep. Innov. Hepatol. 2021;3:100263. doi: 10.1016/j.jhepr.2021.100263. - DOI - PMC - PubMed
    1. Kim D., Murag S., Cholankeril G., Cheung A., Harrison S.A., Younossi Z.M., Ahmed A. Physical Activity, Measured Objectively, Is Associated with Lower Mortality in Patients with Nonalcoholic Fatty Liver Disease. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2021;19:1240–1247.e1245. doi: 10.1016/j.cgh.2020.07.023. - DOI - PubMed
    1. Chalasani N., Younossi Z., Lavine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017;67:328–357. doi: 10.1002/hep.29367. - DOI - PubMed

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