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Endurance exercise rewires liver metabolism differently based on sex, study suggests (opens in a new tab)

medicalxpress.com · 2026-10-01

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Endurance exercise rewires liver metabolism differently based on sex, study suggests

medicalxpress.com · 2026-10-01

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The source study

Endurance exercise elicits temporal and sexual dimorphic multi-omics remodeling of liver metabolism revealed by MoTrPAC

Cell Reports · 2026Open access

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4 claims in this story

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Claim 1 of 4OverstatedNew research from the University of Missouri School of Medicine suggests endurance exercise benefits the liver and metabolism differently in males and females.View evidenceHide evidence

Why this verdict

The abstract supports sex-dimorphic liver metabolic remodeling in male and female rats after endurance exercise, and it reports hepatoprotective molecular signatures. However, as a headline-level claim, this omits the rat-model context and frames the findings broadly as liver/metabolic 'benefits' in males and females, which outruns the abstract-level animal evidence and the story body’s rat-specific framing.

Study evidence

Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) protein complexes across the training time-course.

“we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omics approaches.”

Study evidence

Exercise enhanced liver cholesterol and bile acid synthesis signatures.

“Exercise enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise.”

Claim 2 of 4OverstatedMizzou researchers found endurance exercise altered how liver cells created energy through the Krebs cycle in mitochondria, with female rats showing more proteins created in the energy cycle and male rats showing more proteins modified by a chemical reaction that triggers the cycle.View evidenceHide evidence

Why this verdict

The core sex-dimorphic finding is supported: females showed increased OXPHOS protein complex abundance, while males showed increased acetylation of OXPHOS, TCA-cycle, and fatty-acid oxidation enzymes. But the story’s wording over-specifies and partly distorts the abstract evidence by describing female changes as 'more proteins created' in the Krebs cycle and male acetylation as a chemical reaction that 'triggers the cycle.' The profile supports abundance and acetylation changes, not that acetylation triggers the Krebs cycle or that new protein creation was directly measured as stated.

Study evidence

Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) protein complexes across the training time-course.

“we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omics approaches.”

Study evidence

Exercise induced increased acetylation in male rat livers on proteins of oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid oxidation.

“Mechanistic examination revealed that these sex-specific acetylation events are partially mediated by carnitine acetyltransferase.”

Claim 3 of 4OverstatedExercise training improved liver health in both sexes, including reduced liver fat, improved cholesterol use and disposal, and fewer markers of fibrosis; males specifically seemed to expel more cholesterol from the body than females.View evidenceHide evidence

Why this verdict

Several components are supported: fibrosis/stellate-cell activation markers were reduced in both sexes after 8 weeks, male rats showed reduced liver lipid metabolites, and males had higher fecal cholesterol and cholic acid with exercise. But the story generalizes reduced liver fat and improved cholesterol use/disposal as liver-health improvements in both sexes, whereas the abstract-level profile makes the lipid-metabolite reduction male- and 8-week-specific and treats cholesterol/bile-acid synthesis and fecal excretion as signatures or inferred mechanisms, not direct proof of improved cholesterol disposal in both sexes.

Study evidence

Exercise enhanced liver cholesterol and bile acid synthesis signatures.

“Exercise enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise.”

Study evidence

Male rats exhibited higher fecal cholesterol and cholic acid levels with exercise, consistent with a sex-specific lipid excretion mechanism.

“Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise.”

Claim 4 of 4Not coveredThe researchers said it is still unclear why the adaptations differ by sex and suggested the findings may help guide more personalized interventions for MASLD.View evidenceHide evidence

Why this verdict

The abstract-level profile supports that mechanisms of sex-dependent liver metabolic remodeling are incompletely understood and that carnitine acetyltransferase was only a partial mediator of male-biased acetylation changes. However, the specific quoted statement that 'why these different adaptations occur is still unclear' and the claimed implication for personalized MASLD interventions are not present in the supplied abstract-level profile, so they cannot be verified at this depth.

Study evidence

Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) protein complexes across the training time-course.

“we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omics approaches.”

Study evidence

Exercise induced increased acetylation in male rat livers on proteins of oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid oxidation.

“Mechanistic examination revealed that these sex-specific acetylation events are partially mediated by carnitine acetyltransferase.”

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What the story left out

Important study details the story did not include.

Mechanistic examination implicated carnitine acetyltransferase as a partial mediator of sex-specific hepatic protein acetylation events.
The story says the reasons for the sex differences remain unclear, but it does not mention the paper’s reported partial mechanistic mediator, carnitine acetyltransferase.
From in_vivo_animal

5 things the story did carry across

The study is an in vivo rat endurance-exercise training time-course with liver multi-omics profiling, not a human clinical trial.
Primary finding: sex-dimorphic liver metabolic remodeling, with increased OXPHOS protein complex abundance in females and increased acetylation of OXPHOS/TCA/FAO enzymes in males.
Exercise enhanced hepatic cholesterol and bile-acid synthesis signatures, reduced liver lipid metabolites in males after 8 weeks, and was linked to male fecal cholesterol/cholic-acid excretion signatures.
Eight weeks of training reduced molecular markers related to hepatic stellate-cell activation and fibrosis in both sexes.
Generalizability and translation are limited because the supplied evidence is from rats and does not establish clinical guidance or personalized MASLD interventions.

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study summary

Lead result

in vivo animal

1Lead resultin vivo animalMap temporal (1, 2, 4, 8 weeks) and sex-dimorphic multi-omics remodeling of rat liver metabolism in response to endurance exercise (MoTrPAC), highlighting OXPHOS protein complex abundance changes in females and widespread metabolic enzyme acetylation changes in males.in vivo animal endurance exercise training time-course with liver multi-omics profilingExpand

In plain English

MoTrPAC rat endurance-training time-course (1, 2, 4, 8 weeks) multi-omics analysis of liver reveals sex- and time-dependent molecular remodeling: females show progressive increases in oxidative phosphorylation (OXPHOS) protein complex abundance, while males show increased acetylation of metabolic enzymes (OXPHOS, TCA cycle, fatty acid oxidation); exercise also alters hepatic cholesterol/bile acid synthesis, fecal lipid excretion in males, and reduces markers of hepatic stellate cell activation/fibrosis after 8 weeks.

Key findings

Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) protein complexes across the training time-course.
Male livers showed increased acetylation of OXPHOS, tricarboxylic acid cycle, and fatty acid oxidation enzymes.

“we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omics approaches.”

What this piece can’t prove

Abstract does not provide detailed experimental methods, specific molecular assay parameters, or full mechanistic evidence.

1 further detail could not be confirmed from the summary.

2in vivo animalTest a mechanistic explanation for male-biased exercise-associated hepatic protein acetylation changes by implicating carnitine acetyltransferase as a partial mediator.in vivo animalExpand

In plain English

In trained rats, exercise produces male-biased increases in protein acetylation (including enzymes of OXPHOS, the TCA cycle, and fatty acid oxidation) in liver, and a mechanistic examination reported that these sex-specific acetylation events are at least partially mediated by carnitine acetyltransferase.

Key findings

Exercise induced increased acetylation in male rat livers on proteins of oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid oxidation.
A mechanistic examination implicated carnitine acetyltransferase as a partial mediator of the sex-specific, exercise-associated hepatic protein acetylation events.

“Mechanistic examination revealed that these sex-specific acetylation events are partially mediated by carnitine acetyltransferase.”

What this piece can’t prove

4 further details could not be confirmed from the summary.

3in vivo animalCharacterize exercise effects on hepatic cholesterol/bile acid synthesis and lipid metabolites, and link these to sex-specific lipid excretion signatures in feces (cholesterol and cholic acid).in vivo rat endurance exercise; liver metabolomics/lipidomicsExpand

In plain English

In male and female rats subjected to endurance exercise across 1, 2, 4, and 8 weeks, exercise was associated with increased hepatic cholesterol and bile acid synthesis signatures and a reduction in liver lipid metabolites that was prominent in males after 8 weeks; males also showed higher fecal cholesterol and cholic acid, consistent with a sex-specific lipid excretion signature.

Key findings

Exercise enhanced liver cholesterol and bile acid synthesis signatures.
Eight weeks of exercise reduced liver lipid metabolites in males.

“Exercise enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise.”

What this piece can’t prove

Cholesterol/bile acid 'synthesis' conclusions appear to be based on pathway or signature inference rather than direct metabolic flux measurements.
Temporal specificity (notably the 8-week male effect) is reported, but the abstract does not detail intermediate timepoint trajectories or variability.
Findings are from an in vivo rat endurance exercise model and may not directly translate to other species without further validation.

1 further detail could not be confirmed from the summary.

4in vivo animalCharacterize exercise effects on hepatic cholesterol/bile acid synthesis and lipid metabolites, and link these to sex-specific lipid excretion signatures in feces (cholesterol and cholic acid).in vivo animal fecal lipid/bile-acid quantificationExpand

In plain English

In MoTrPAC rats subjected to endurance exercise, targeted fecal measurements reported higher cholesterol and cholic acid levels in males versus females, interpreted as a sex-specific lipid excretion signature that complements hepatic cholesterol/bile acid remodeling.

Key findings

Male rats exhibited higher fecal cholesterol and cholic acid levels with exercise, consistent with a sex-specific lipid excretion mechanism.

“Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise.”

What this piece can’t prove

4 further details could not be confirmed from the summary.

5in vivo animalAssess whether 8 weeks of endurance training reduces molecular markers related to hepatic stellate cell activation and fibrosis in both sexes (hepatoprotective signature).rat endurance exercise intervention (8-week endpoint), sex-stratifiedExpand

In plain English

In a MoTrPAC multi-omics study of male and female rats, 8 weeks of endurance exercise was reported to reduce molecular markers related to hepatic stellate cell activation and fibrosis in both sexes, which the authors interpret as part of an exercise-induced hepatoprotective signature.

Key findings

Eight weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes.

“Eight weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes.”

What this piece can’t prove

Evidence is limited to the abstract; methods and detailed results for fibrosis-related endpoints are not provided.
Unclear whether molecular marker changes correspond to histological or functional improvement in liver fibrosis.

2 further details could not be confirmed from the summary.

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