Evidence map›Paper›PMID 33898958›Full record

ArticleJHEP reports : innovation in hepatology2021

Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD.

Sechang Oh, Takehiko Tsujimoto, Bokun Kim, Fumihiko Uchida, Hideo Suzuki, Seiichiro Iizumi, Tomonori Isobe, Takeji Sakae, Kiyoji Tanaka, Junichi Shoda

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 43 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 6 pooled it
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06359444 naunknown statusnot on this mapstarted 2024, after this paper: background citation

Effect of High Intensity Exercise Rehabilitation on Hepatic Fatty Acids (Liver Function), Insulin Sensitivity and Cardiovascular Risk in Patients With MASLD

TypeinterventionalSponsorUniversity GhentRan2024 to 2026Enrolled92ConditionsExercise Therapy, Metabolic Dysfunction-associated Steatotic Liver DiseaseArmsCombined aerobic + strength training, Combined strength + HIIT training
NCT06682663 nanot yet recruitingnot on this mapstarted 2024, after this paper: background citation

Evaluation of the Effect of Live Streaming Exercise on the Improvement of Hepatic Steatosis and Fibrosis in Pregnant Women with MASLD and Its Study Based on the Liver-gut Axis Mechanism.

TypeinterventionalSponsorPeking UniversityRan2024 to 2026Enrolled220ConditionsMetabolic Dysfunction-associated Steatotic Liver DiseaseArmsLive Streaming Exercise
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 6 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
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  14. Physical exercise in liver diseases.Hepatology (Baltimore, Md.) · 2026
    Review
  15. Article
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  17. Review
  18. Article
  19. Review
  20. Inflammation-Insulin Resistance Crosstalk and the Central Role of Myokines.International journal of molecular sciences · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Sechang OhFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Takehiko TsujimotoFaculty of Human Sciences, Shimane University, Shimane, Japan.
Bokun KimDepartment of Sports Health Care, Inje University, Gimhae, Republic of Korea.
Fumihiko UchidaDepartment of Oral and Maxillofacial Surgery, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
Hideo SuzukiFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Seiichiro IizumiDoctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Tomonori IsobeFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Takeji SakaeFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Kiyoji TanakaFaculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Junichi ShodaFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
University of Tsukuba · JPInje University · KRShimane University · JPUniversity of Tsukuba Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsA weight-loss-independent beneficial effect of exercise on non-alcoholic fatty liver disease (NAFLD) management has been reported, but the underlying mechanism is unknown. To help determine this mechanism, the effects of exercise on individual tissues (liver, adipose tissue, and skeletal muscle) were retrospectively studied.

methodsData from Japanese obese men with NAFLD in a 3-month exercise regimen were analysed and compared with those in a 3-month dietary restriction program designed to achieve weight loss. The underlying mechanism was studied in a smaller subcohort.

resultsIndependent of the effect of weight loss, the exercise regimen reduced liver steatosis by 9.5% and liver stiffness by 6.8% per 1% weight loss, and resulted in a 16.4% reduction in FibroScan-AST score. Improvements in these hepatic parameters were closely associated with anthropometric changes (reduction in adipose tissue and preservation of muscle mass), increases in muscle strength (+11.6%), reductions in inflammation and oxidative stress (ferritin: -22.3% and thiobarbituric acid: -12.3%), and changes in organokine concentrations (selenoprotein-P: -11.2%, follistatin: +17.1%, adiponectin: +8.9%, and myostatin: -21.6%) during the exercise regimen. Moreover, the expression of target genes of the transcription factor Nrf2, an oxidative stress sensor, was higher in monocytes, suggesting that Nrf2 is activated. Large amounts of high-intensity exercise were effective at further reducing liver steatosis and potentiating improvements in pathophysiological parameters (liver enzyme activities and organokine profiles).

conclusionsThe weight-loss-independent benefits of exercise include anti-steatotic and anti-stiffness effects in the livers of patients with NAFLD. These benefits seem to be acquired through the modification of inter-organ crosstalk, which is characterised by improvements in organokine imbalance and reductions in inflammation and oxidative stress. LAY SUMMARY: We investigated the effects of exercise on non-alcoholic fatty liver disease (NAFLD) that were not related to weight loss. We found that exercise had considerable weight-loss-independent benefits for the liver through a number of mechanisms. This suggests that exercise is important for NAFLD patients, regardless of whether they lose weight.

Indexed as

Aerobic exerciseALT, alanine aminotransferaseANGPTL6, angiopoietin-like 6AST, aspartate aminotransferaseBDNF, brain-derived neurotrophic factorCAP, controlled attenuation parameterDietary restrictionElarge, large amount of exercise groupEsmall, small amount of exercise groupEsub, exercise (subset for which biological samples were available) groupEtotal, exercise groupFAST-Score, FibroScan-AST scoreFGF-21, fibroblast growth factor-21FPG, fasting plasma glucoseGCLC, glutamate-cysteine ligase catalytic subunitGCLM, glutamate-cysteine ligase modifier subunitGGT, gamma-glutamyl transpeptidaseGPx, glutathione peroxidaseHepatokineHO1, heme oxygenase 1HOMA-IR, homeostasis model assessment-insulin resistanceKC, Kupffer cellsLiver fatLiver stiffnessLPS, lipopolysaccharideLSM, liver stiffness measured using transient elastographymnSOD, manganese superoxide dismutaseMVPA, moderate-to-vigorous intensity physical activityMyokineNAFLD, non-alcoholic fatty liver diseaseNASH, non-alcoholic steatohepatitisNEFAs, non-esterified fatty acidsNF-Score, NAFLD fibrosis scoreNQO1, NAD(P)H quinone oxidoreductaseNrf2, nuclear factor E2-related factor 2Nuclear factor-erythroid 2-related factor 2PBMCs, peripheral blood mononuclear cellsSe-P, selenoprotein-PSPARC, secreted protein acidic and rich in cysteineTBARS, thiobarbituric acid-reactive substancesTEI, total energy intakeTG, triglyceridesTNF-α, tumour necrosis factor alphaVAT, visceral adipose tissueWC, waist circumferenceWFA+-M2BP, Wisteria floribunda agglutinin-positive human Mac-2 binding proteinWsub, weight-loss (subset for which biological samples were available) groupWtotal, weight-loss group

Identifiers

PMID33898958
PMCPMC8059085
OpenAlexW3127779032

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.