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

Qi Li, Zhi Jia, Musi Ji, Bayaer Nashun

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.