Postprandial Hyperglycemia Stimulates Neuroglial Plasticity in Hypothalamic POMC Neurons after a Balanced Meal

Nuzzaci, Danaé; Cansell, Céline; Liénard, Fabienne; Nédélec, Emmanuelle; Fradj, Selma Ben; Castel, Julien; Foppen, Ewout; Denis, Raphaël; Grouselle, Dominique; Laderrière, Amélie; Lemoine, Aleth; Mathou, A.; Tolle, Virginie; Heurtaux, Tony; Fioramonti, Xavier; Audinat, Etienne; Pénicaud, Luc; Nahon, Jean‐Louis; Rovère, Carole; Bénani, Alexandre

doi:10.1016/j.celrep.2020.02.029

Cited by 37 publications

(28 citation statements)

References 79 publications

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“…Moreover, we provided novel evidence that acute exposure to HFD specifically increases GFAP mRNA levels in HT within the first hours of food consumption. This mechanism might contribute to the postprandial astrocytic remodeling that happens after a balanced meal (Nuzzaci et al, 2020). Another observation worth highlighting is that the IL‐6 gene response to food exposure is modulated by GFAP‐positive cells in a differential way, depending on the diet.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, at this stage, while it seems difficult to definitely conclude whether GFAP‐positive glial cell activation or inhibition mediates HFD‐induced HT remodeling, our results clearly support GFAP‐positive glial cell involvement in this process. In a recent work, we reported efficiency of this tool to alter cAMP levels in astrocytes (Nuzzaci et al, 2020). Thus, postprandial changes in cytokines expression involve cAMP signaling.…”

Section: Discussionmentioning

confidence: 99%

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Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein‐positive cells and microglia in male mice

Cansell

Stobbe

Sanchez

et al. 2020

Glia

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In humans, obesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hr of highfat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight. Here, we sought to characterize the postprandial HT inflammatory response to 1, 3, and 6 hr of exposure to either a standard diet (SD) or HFD. HFD exposure increased gene expression of astrocyte and microglial markers (glial fibrillary acidic protein [GFAP] and Iba1, respectively) compared to SD-treated mice and induced morphological modifications of microglial cells in HT. This remodeling was associated with higher expression of inflammatory genes and differential regulation of hypothalamic neuropeptides involved in energy balance regulation. DREADD and PLX5622 technologies, used to modulate GFAP-positive or microglial cells activity, respectively, showed that both glial cell types are involved in hypothalamic postprandial inflammation, with their own specific kinetics and reactiveness to ingested foods. Thus, recurrent exacerbated postprandial inflammation in the brain might promote obesity and needs to be characterized to address this worldwide crisis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein‐positive cells and microglia in male mice

Cansell

Stobbe

Sanchez

et al. 2020

Glia

Self Cite

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“…In a more recent study, the concept of astrocytes tuning to a melanocortinergic tone in response to glucose availability was examined. Nuzzaci et al 57 provided evidence suggesting that the retraction of glial processes is paramount for postprandial synaptic plasticity of POMC neurones, a dynamic process dependent on hyperglycaemia. In conjunction, these findings further add to the rapidly growing body of literature suggesting that astroglia-neuronal networks in the brain operate in close and reciprocal cooperation with the pancreatic islet in order to maintain whole-body glucose homeostasis.…”

Section: Glucose Sensing In Hypothalamic Astrocytesmentioning

confidence: 99%

Insulin action on astrocytes: From energy homeostasis to behaviour

González-García

Gruber

García‐Cáceres

2021

J Neuroendocrinology

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Subsequent to the discovery of insulin in 1921 by F. Banting and C. H. Best, the physiological actions of this hormone have been scrupulously investigated. The initial functional characterisation was focused on insulin action in peripheral tissues (eg, effects on glucose uptake, gluconeogenesis, glycogenolysis, lipolysis and growth promotion, amongst others). Yet, insulin receptors are also widely expressed in the mammalian brain, [1][2][3][4][5][6][7] where their crucial role in the regulation of glucose homeostasis, feeding behaviour, cognition and mood is now recognised.Seminal studies previously reported the anorectic effect of insulin followed by a body weight loss 8 and its direct effect in the regulation of hypothalamic neuropeptides (ie, up-regulation of agouti-related peptide [AgRP] and neuropeptide Y [NPY] and downregulation of pro-opiomelanocortin [POMC] and cocaine-and amphetamine-regulated trasnscript), 9-12 although it was not until the pioneering studies led by Brüning and collaborators with the

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“…Furthermore, a recent study suggested that astrocytic insulin signaling regulates hypothalamic glucose sensing and systemic glucose metabolism ( 94 ). Also, astrocytes in the MBH can respond to acute changes in nutritional exposure, with morphological changes after overnight fasting ( 91 ), or as soon as 1-hr post-prandially ( 95 ). Interestingly, post-prandial retraction of astrocytes surrounding POMC neurons was only seen with standard chow diet, but not HFD ( 95 ).…”

Section: Integration Of Lipid Signals By the Mediobasal Hypothalamus (Mbh)mentioning

confidence: 99%

Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis

2021

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In mammals, myeloid cells help maintain the homeostasis of peripheral metabolic tissues, and their immunologic dysregulation contributes to the progression of obesity and associated metabolic disease. There is accumulating evidence that innate immune cells also serve as functional regulators within the mediobasal hypothalamus (MBH), a critical brain region controlling both energy and glucose homeostasis. Specifically, microglia, the resident parenchymal myeloid cells of the CNS, play important roles in brain physiology and pathology. Recent studies have revealed an expanding array of microglial functions beyond their established roles as immune sentinels, including roles in brain development, circuit refinement, and synaptic organization. We showed that microglia modulate MBH function by transmitting information resulting from excess nutrient consumption. For instance, microglia can sense the excessive consumption of saturated fats and instruct neurons within the MBH accordingly, leading to responsive alterations in energy balance. Interestingly, the recent emergence of high-resolution single-cell techniques has enabled specific microglial populations and phenotypes to be profiled in unprecedented detail. Such techniques have highlighted specific subsets of microglia notable for their capacity to regulate the expression of lipid metabolic genes, including lipoprotein lipase (LPL), apolipoprotein E (APOE) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). The discovery of this transcriptional signature highlights microglial lipid metabolism as a determinant of brain health and disease pathogenesis, with intriguing implications for the treatment of brain disorders and potentially metabolic disease. Here we review our current understanding of how changes in microglial lipid metabolism could influence the hypothalamic control of systemic metabolism.

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Postprandial Hyperglycemia Stimulates Neuroglial Plasticity in Hypothalamic POMC Neurons after a Balanced Meal

Cited by 37 publications

References 79 publications

Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein‐positive cells and microglia in male mice

Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein‐positive cells and microglia in male mice

Insulin action on astrocytes: From energy homeostasis to behaviour

Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis

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