Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation

Abstract

Previous studies identify a role for hypothalamic glia in energy balance regulation; however, a narrow hypothalamic focus provides an incomplete understanding of how glia throughout the brain respond to and regulate energy homeostasis. We examined the responses of glia in the dorsal vagal complex (DVC) to the adipokine leptin and high fat diet-induced obesity. DVC astrocytes functionally express the leptin receptor; in vivo pharmacological studies suggest that DVC astrocytes partly mediate the anorectic effects of leptin in lean but not diet-induced obese rats. Ex vivo calcium imaging indicated that these changes were related to a lower proportion of leptin-responsive cells in the DVC of obese versus lean animals. Finally, we investigated DVC microglia and astroglia responses to leptin and energy balance dysregulation in vivo: obesity decreased DVC astrogliosis, whereas the absence of leptin signaling in Zucker rats was associated with extensive astrogliosis in the DVC and decreased hypothalamic micro-and astrogliosis. These data uncover a novel functional heterogeneity of astrocytes in different brain nuclei of relevance to leptin signaling and energy balance regulation.

Hypothalamic REV-ERB nuclear receptors control diurnal food intake and leptin sensitivity in diet-induced obese mice

“…One of these, FABP7, has been proposed to function in glial cells within the ARC to impair leptin signaling especially on HFD 34 . Several studies demonstrated a key role of glial cells on leptin and feeding regulation by the hypothalamus [53][54][55][56][57][58] .…”

Insulin action on astrocytes: From energy homeostasis to behaviour

“…46 In addition, studies carried out on rats have highlighted that that DVC astrocytes partly mediate the anorectic effects of leptin and pharmacological glucagonlike peptide-1 receptor ligands. 47,48 Overall, these findings suggest that NTS astrocytes are involved in the integration of peripheral satiety signals to control feeding behaviour.…”

A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism

“…Because ventilation must parallel energy expenditure for arterial blood gas homeostasis, there must be areas of the CNS in which the circuitry controlling these two systems converge. NTS LepRb neurons and glia contribute to interactions of energy balance with gastrointestinal (GI) satiation signaling (Myers et al, 2009;Hayes et al, 2010;Stein et al, 2020). Because the NTS is also a major chemosensitive area that regulates breathing (Nattie, 2001;Huda et al, 2012), it appears ideally suited to harmonize these multiple functions with body-mass-related respiratory control and CO 2 chemosensitivity.…”