Abstract
Under high-fat feeding, the hypothalamus atypically undergoes pro-inflammatory signaling activation. Recent data from transcriptomic analysis of microglia from rodents and humans has allowed the identification of several microglial subpopulations throughout the brain. Numerous studies have clarified the roles of these cells in hypothalamic inflammation, but how each microglial subset plays its functions upon inflammatory stimuli remains unexplored. Fortunately, these data unveiling microglial heterogeneity have triggered the development of novel experimental models for studying the roles and characteristics of each microglial subtype. In this review, we explore microglial heterogeneity in the hypothalamus and their crosstalk with astrocytes under high fat diet–induced inflammation. We present novel currently available ex vivo and in vivo experimental models that can be useful when designing a new research project in this field of study. Last, we examine the transcriptomic data already published to identify how the hypothalamic microglial signature changes upon short-term and prolonged high-fat feeding.
Highlights
We examine the subtypes of microglia that may be involved in high-fat diet (HFD)-induced hypothalamic inflammation and investigate how these cells interact with astrocytes upon high-fat feeding
Magnetic-activated cell sorting (MACS) [130] and fluorescenceactivated cell sorting (FACS) [131,132] using these fluorescent reporter mice or even microglia-specific surface markers allow the physical isolation of various subsets of microglia, which can be obtained from primary cultures or co-cultures with other cells
The authors initially analyzed microglia and central nervous system (CNS)-associated macrophage (CAM) signatures obtained from scRNA-seq, during homeostasis and disease, and identified beta-hexosaminidase subunit beta (Hexb) as a stably expressed microglia core gene
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Hypothalamic inflammation is a condition frequently observed in experimental models of diet-induced obesity (DIO) [1,2,3] and obese humans [4,5,6] This inflammatory response is mainly triggered by excessive saturated fatty acids (SFAs) from the diet [7,8,9], which reach the neural tissue mainly through the median eminence (ME), where fenestrated vascular endothelium lacks a blood–brain barrier (BBB) [10,11]. Brain perivascular macrophages (PVMs) react to excessive free fatty acids (FFAs) circulating in the blood vessels, with a consequent increase in BBB permeability [12,13] Glial cells, such as astrocytes and microglia, quickly sense and react to the presence of those SFAs in the hypothalamic parenchyma, releasing pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS) [14,15]. We investigate novel transcriptomic data already published to clarify how the hypothalamic microglia signature changes under saturated fat consumption
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