Microglia are Required for Developmental Specification of AgRP Innervation in the Hypothalamus of Offspring Exposed to Maternal High Fat Diet During Lactation.

Maternal high fat diet exposure results in enhanced risk for negative health outcomes in humans and multiple animal models. Here we demonstrate that microglia are required for changes in body weight and perturbations to hypothalamic circuits caused by maternal high fat diet exposure that is limited to the lactational period. We identified spatially and temporally limited morphological changes to microglia that reflect an enhancement of surveillance activity and align with a critical period of hypothalamic circuit formation. We also identify direct cellular interactions between microglia and developing axons, as well as evidence for synaptic engulfment, although this mechanism does not appear to be responsible for changes to neural patterning caused by maternal high fat diet exposure. Together these findings identify an essential role for microglia in specifying patterns of hypothalamic innervation during development in response to maternal high fat diet exposure, which may contribute to developmental programming of metabolic phenotype.