The long-term impact of obesity in pregnancy on offspring hypothalamic feeding pathways.

An accumulating body of evidence shows that offspring exposure to maternal obesity in the peri-natal period causes an increased risk to develop obesity later in life. Animal models have demonstrated that increased weight gain in offspring exposed to maternal obesity is preceded by increased food intake, implicating altered brain control of food intake as a likely cause. The hypothalamus is crucial for regulating feeding behaviour and energy homeostasis. This article reviews findings from human and animal studies to provide an updated perspective on how maternal obesity alters fetal hypothalamic development, predisposing offspring to long-term metabolic dysfunction. We discuss how maternal obesity impacts on hypothalamic development and the key molecular mechanisms, including epigenetic modifications, hormonal disruption, neuroinflammation and gut-brain axis interactions, which may mediate these changes. We highlight the critical gaps that remain in understanding the specific molecular pathways driving neurodevelopmental alterations in offspring, as well as emerging areas of research, including the role of extracellular vesicles in maternal-fetal communication. An in depth understanding of the molecular mechanisms that mediate the link between maternal metabolic state and offspring hypothalamic control of feeding is crucial in informing public health policies and clinical interventions aimed at reducing the intergenerational transmission of obesity.