Poormoghadam, D. | bioRxiv Science

bioRxiv2024

Limited microglial metabolic improvement with time-restricted feeding in diet-induced obesity

Time-restricted eating has shown promise for improving metabolic health in obese humans via incompletely resolved mechanisms. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects microglial immunometabolism using Wistar rats. We found that in high-fat diet (HFD)-fed obese rats, TRF during the active phase reduced fat mass, altered rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglia. These effects were dampened or absent with TRF during the resting phase. However, a HFD-induced microglial immunometabolic phenotype, characterized by reduced electron transport chain and increased lipid metabolism gene expression, and metabolic inflexibility, was not reversed by TRF in either the active or resting phase, indicating that reprogrammed microglial metabolism in obesity is a persistent cellular functional change that requires further study.

immunology↗

bioRxiv2023

An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptional and functional types

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signalling, outflow of the autonomic nervous system, and projections to other brain areas. The past years, single-cell datasets of the hypothalamus have contributed immensely to the current understanding of the diverse hypothalamic cellular composition. While the PVN has been adequately classified functionally, its molecular classification is currently still insufficient. To address this, we created a detailed atlas of PVN transcriptional cell types by integrating various PVN single-cell datasets into a recently published hypothalamus single-cell transcriptome atlas. Furthermore, we functionally profiled transcriptional cell types, based on relevant literature, existing retrograde tracing data and existing single-cell data of a PVN-projection target region. In our PVN atlas dataset, we identify the well-known different neuropeptide types, each composed of multiple novel subtypes. We identify Avp-Tac1, Avp-Th, Oxt-Foxp1, Crh-Nr3c1 and Trh-Nfib as the most important neuroendocrine subtypes based on markers described in literature. To characterize the pre-autonomic functional population, we integrated a single-cell retrograde tracing study of spinally-projecting pre-autonomic neurons into our PVN atlas. We identify these (pre-sympathetic) neurons to co-cluster with the Adarb2 + clusters in our dataset. Finally, we identify expression of receptors for Crh, Oxt, Penk, Sst, and Trh in the dorsal motor nucleus of the vagus, a key region that pre-parasympathetic PVN neurons project to. Concluding, our study present a detailed overview of the transcriptional cell types of the murine PVN, and provides a first attempt to resolve functionality for the identified populations.

neuroscience↗