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Study · Measured the body's own peptide · 2025

1 result

Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD.

Heldens A, Antwi M, Onghena L, Meese T, Gansemans Y, Smet J, Dupont E, Verhelst X, Raevens S, Van Vlierberghe H, Vanlander A, Van Nieuwerburgh F and 4 more

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Devisscher L, De Bruyne R, Geerts A, Lefere S

JHEP reports : innovation in hepatology29 Mar 2025Cited by 5 (Europe PMC)

PMID40496439 (opens in a new tab)PMCIDPMC12151218 (opens in a new tab)DOI10.1016/j.jhepr.2025.101404 (opens in a new tab)PepBankPUB-40496439
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Summary

Background & aimsAlthough maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal Western diet (WD) on MASLD progression, and test drug candidates.MethodsFemale mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 24 days, 10 weeks, and 16 weeks (n = 5-11 per group). Additionally, offspring from dams with hepatic insulin receptor knockout were evaluated (n = 9-12 per group). Serum fibroblast growth factor 21 (FGF21) and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) were measured in adolescents with MASLD with or without a history of maternal obesity. The therapeutic efficacy of FGF21, semaglutide and an amylin analogue was assessed from 8 to 16 weeks of age (n = 8-12 per group).ResultsStarting from weaning age, maternal WD feeding aggravated body weight gain, insulin resistance, steatosis, and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Isolated maternal hepatic insulin resistance partially recapitulated offspring inflammation and fibrosis. Notably, OXPHOS was also downregulated in a transcriptomic dataset of maternal WD feeding in non-human primates. Serum FGF21 and MOTS-c correlated with MASLD severity and maternal obesity in adolescents. Particularly FGF21 treatment ameliorated steatohepatitis and mitochondrial function.ConclusionsMaternal WD aggravates MASLD in male offspring starting from weaning age, with mitochondrial dysfunction contributing to disease severity. This was reversed by FGF21 agonism.Impact and implicationsThe underlying mechanisms of maternal obesity contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) severity in the offspring are not completely understood. Our study characterises the impact of multigenerational maternal Western diet on offspring MASLD development and identifies mitochondrial dysfunction as a contributor to disease severity. In this setting, pharmacological compounds targeting mitochondrial dysfunction appear to have the greatest therapeutic potential.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 01HumanEndogenous levelObservational studyOther

    In adolescents with MASLD, serum MOTS‑c correlated with MASLD severity and with a history of maternal obesity.

    In plain wordsIn adolescents with fatty liver disease, the body's own MOTS‑c levels were linked to disease severity and to maternal obesity.

    Peptide
    MOTS-c
    Outcome
    Direction not reportedSerum MOTS-c correlation with MASLD severity and maternal obesity
    Study

    n: not reported in source

    Outcome group
    Mitochondrial function · Liver

    Source sentences

    Summary
    Serum FGF21 and MOTS-c correlated with MASLD severity and maternal obesity in adolescents.
    1 context sentence
    Summary · context
    Serum fibroblast growth factor 21 (FGF21) and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) were measured in adolescents with MASLD with or without a history of maternal obesity.

    This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:06 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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