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Research progress on the association of maternal high-fat diet with offspring neurodevelopment and susceptibility to Parkinson's disease.

Front Nutr · 2026-07-24

DOI: 10.3389/fnut.2026.1907443PMID: 42568402

Open accessreview-article; Review; Journal ArticleOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Maternal high-fat diet (mHFD) is a growing global nutritional concern during pregnancy. It induces maternal systemic low-grade inflammation and oxidative stress, reshaping the intrauterine milieu via the placenta and causing selective developmental impairments in offspring midbrain dopaminergic (DA) neurons-including aberrant precursor proliferation/differentiation, simplified synapses, and nigrostriatal circuit deficits-which may increase adulthood Parkinson's disease (PD) susceptibility. Mechanistically, mHFD acts through two synergistic pathways: persistent activation of the insulin resistant-NF-κB inflammatory axis and suppression of PINK1/Parkin-mediated mitophagy, mutually reinforcing and compromising DA neuron resilience. This article reviews the pathological process of mHFD-mediated remodeling of the intrauterine microenvironment to increase the susceptibility of offspring PD and its two core mechanism pathways: the continuous activation of the IR-NF-κB inflammatory pathway and the functional inhibition of the PINK1/Parkin-mediated mitophagy pathway. On this basis, multi-dimensional early warning markers based on inflammatory factors, mitophagy-related molecules, epigenetic markers and nutritional exposure indicators, as well as potential intervention strategies such as nutritional supplementation, anti-inflammatory and pro-mitophagy targeting the above pathways were summarized, in order to provide a theoretical reference for the primary prevention of PD.

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