# Comparative effects of different loads of aerobic exercise on lipid metabolism in MASLD rats: a perspective from the gut-liver axis

**Authors:** Deng Dongkun, Jiang Qingfeng, Li Chang, Lin Yunhua, Shi Jiaming, Liu Yufei, Xu Lin

PMC · DOI: 10.3389/fmed.2025.1609751 · 2025-07-15

## TL;DR

This study explores how different intensities of aerobic exercise affect liver health in rats with fatty liver disease, focusing on gut and liver interactions.

## Contribution

The study identifies optimal aerobic exercise loads for improving MASLD through the gut-liver axis and provides molecular insights into the mechanisms.

## Key findings

- Medium- and high-load aerobic exercise improved lipid metabolism dysfunction more effectively than low-load exercise in MASLD rats.
- Aerobic exercise restored gut barrier function and balanced gut-liver homeostasis in MASLD rats.
- High-load aerobic exercise upregulated bile acid-related genes and modulated butyrate-producing gut bacteria.

## Abstract

Exercise training has been shown to be effective in ameliorating obesity-related diseases, but the therapeutic effects of different loads of exercise on metabolic dysfunction-associated steatotic liver disease (MASLD) as well as the underlying mechanisms by which exercise is based on the enterohepatic axis and thus alleviates MASLD are still unclear. Therefore, the present study aimed to clarify the optimal exercise load for improving MASLD and to reveal its molecular mechanisms in the treatment of metabolic-associated fatty liver disease (MASLD) in the context of the enterohepatic axis.

Forty male rats were randomly divided into two groups: NFD (n = 8) and HFD (n = 32). The rats in the NFD group were fed a normal chow, while those in the HFD group were fed a high-fat chow. Following an eight-week period of observation, the rats in the high-fat diet (HFD) group were separated into four further groups for the purpose of analysis: (1) LEH (low-load aerobic exercise)-8; (2) MEH (medium-load aerobic exercise)-8; (3) HEH (high-load aerobic exercise)-8; and (4) HFD-8. At the conclusion of the experiment, blood, liver, and ileum samples were collected for analysis of the rats’ baseline conditions, hepatic lipid metabolism, bile acid pathway and gut microbiota, and synthesis of analyses.

The development of lipid metabolism disorders, insulin resistance, and hepatic steatosis in MASLD rats was improved to different degrees in all three exercise modes. It also restored the high-fat diet (HFD)-induced intestinal barrier dysfunction and balanced the homeostasis of the gut-liver axis. Aerobic exercise also upregulated bile acid-related gene expression modulated butyrate-producing bacterial taxa, and adjusted the abundance of butyrate-generating bacteria.

Compared with low-load aerobic exercise, medium- and high-load aerobic exercise was more beneficial in modulating lipid metabolism dysfunction in MASLD rats, and to some extent, high-load aerobic exercise was superior to medium-load aerobic exercise.

## Linked entities

- **Diseases:** metabolic dysfunction-associated steatotic liver disease (MONDO:0013209), MASLD (MONDO:0013209)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 78968] {aka ADD-1, ADD1, SREBP-1, SREBP-1c, Srebp1}, Cyp2e1 (cytochrome P450, family 2, subfamily e, polypeptide 1) [NCBI Gene 25086] {aka Cyp2e}, Nr1h3 (nuclear receptor subfamily 1, group H, member 3) [NCBI Gene 22259] {aka LXR, RLD1, Unr1}, Acc (anterior capsular cataract) [NCBI Gene 104371], Cpt1a (carnitine palmitoyltransferase 1a, liver) [NCBI Gene 12894] {aka C730027G07, CPTI, Cpt1}, Slc10a1 (solute carrier family 10 member 1) [NCBI Gene 24777] {aka Ntcp, Ntcp1, SBACT}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 25747] {aka PPAR}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 81646] {aka Creb}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Nr1h4 (nuclear receptor subfamily 1, group H, member 4) [NCBI Gene 60351] {aka Fxr}, Lep (leptin) [NCBI Gene 25608] {aka OB, obese}, Abcb11 (ATP binding cassette subfamily B member 11) [NCBI Gene 83569] {aka Bsep, Spgp}, NR1H3 (nuclear receptor subfamily 1 group H member 3) [NCBI Gene 10062] {aka LXR-a, LXRA, RLD-1}, Nr0b2 (nuclear receptor subfamily 0, group B, member 2) [NCBI Gene 117274] {aka Shp}, Ocln (occludin) [NCBI Gene 83497], Angptl4 (angiopoietin-like 4) [NCBI Gene 362850], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Fasn (fatty acid synthase) [NCBI Gene 14104] {aka A630082H08Rik, FAS}, Actb (actin, beta) [NCBI Gene 81822] {aka Actx}, Tjp1 (tight junction protein 1) [NCBI Gene 292994] {aka ZO-1}, Cldn1 (claudin 1) [NCBI Gene 65129], Cyp2e1 (cytochrome P450, family 2, subfamily e, polypeptide 1) [NCBI Gene 13106] {aka CYPIIE1, Cyp2e}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}, Nr1h3 (nuclear receptor subfamily 1, group H, member 3) [NCBI Gene 58852] {aka LXRalpha}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, Acaca (acetyl-CoA carboxylase alpha) [NCBI Gene 60581] {aka ACC1, Acac}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 20787] {aka ADD1, SREBP1, bHLHd1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}
- **Diseases:** microbial disorders (MESH:D015163), NAFLD (MESH:D065626), hepatic lipid degeneration (MESH:D011017), Liver Diseases (MESH:D008107), weight loss (MESH:D015431), abnormalities of glucose tolerance (MESH:D018149), malignancy (MESH:D009369), inflammation (MESH:D007249), metabolic abnormality-associated steatohepatopathy (MESH:D008659), endotoxemia (MESH:D019446), hepatic steatosis (MESH:D005234), Abnormal lipid metabolism (MESH:D052439), DD (MESH:C536170), insulin resistance (MESH:D007333), adiposity (MESH:D018205), dyslipidemia (MESH:D050171), obese (MESH:D009765), weight gain (MESH:D015430)
- **Chemicals:** BA (MESH:D001647), butyric acid (MESH:D020148), butyrate (MESH:D002087), eosin (MESH:D004801), HEH (MESH:C037834), MDA (MESH:D015104), Lipid (MESH:D008055), LPS (MESH:D008070), H&amp;E (MESH:D006371), TG (MESH:D014280), SDS (MESH:D012967), oil red O (MESH:C011049), BCA (MESH:C047117), water (MESH:D014867), polyacrylamide (MESH:C016679), fatty acid (MESH:D005227), nitrogen (MESH:D009584), malondialdehyde (MESH:D008315), Blood glucose (MESH:D001786), paraffin (MESH:D010232), ether (MESH:D004986), haematoxylin (MESH:D006416), PVDF (MESH:C024865), fat (MESH:D005223), DAB (-), formaldehyde (MESH:D005557), choline (MESH:D002794), lipid peroxides (MESH:D008054), Tween-20 (MESH:D011136), cholesterol (MESH:D002784), Glucose (MESH:D005947), saline (MESH:D012965)
- **Species:** Bacteroidia (class) [taxon 200643], Fusobacteriota (phylum) [taxon 32066], Allobaculum (genus) [taxon 174708], Bacillus (genus) [taxon 55087], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Clostridia (class) [taxon 186801], Oscillibacter (genus) [taxon 459786], Lachnospiraceae (family) [taxon 186803], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Clostridium (genus) [taxon 1485], gut metagenome (species) [taxon 749906], Prevotellaceae (family) [taxon 171552], Homo sapiens (human, species) [taxon 9606], Ruminococcaceae [taxon 541000], Colidextribacter (genus) [taxon 1980681]
- **Mutations:** 5A-C

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12305809/full.md

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Source: https://tomesphere.com/paper/PMC12305809