Hypothalamic astrocytes control systemic glucose metabolism and energy balance

Chao, Daniela Herrera Moro; Kirchner, Matthew K.; Pham, Cuong; Foppen, Ewout; Denis, R.; Castel, Julien; Morel, Chloé; Montalban, Enrica; Hassouna, Rim; Bui, Linh‐Chi; Renault, Justine; Mouffle, Christine; García‐Cáceres, Cristina; Tschöp, Matthias H.; Li, Dongdong; Martin, Claire; Stern, Javier E.; Luquet, Serge

doi:10.1016/j.cmet.2022.09.002

Cited by 45 publications

(36 citation statements)

References 74 publications

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“…Even though there is a variety of tools to increase astrocyte Ca 2+ signaling, till recently, IP 3 R2 −/− mice and IP3 sponges (Agulhon et al, 2008;Petravicz et al, 2008) have been the only available options to achieve astrocyte Ca 2+ selective attenuation. Recent studies have provided new tools to lessen intracellular Ca 2+ release, such as activation of kappa-opioid receptor coupled to a Gi-GPCR selectively activated by salvinorin B (Vardy et al, 2015;Herrera Moro Chao et al, 2022) or by Cre-dependent expression of hPMCA2, a human plasma membrane Ca 2+ ATPase pump that constitutively extrudes Ca 2+ from astrocytes (Yu et al, 2018(Yu et al, , 2021. Decreases in astrocyte intracellular Ca 2+ levels have also been observed during neuropathology after astrocyte Gs-GPCR activation (Pham et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The evolving genetically targeted optical and pharmacological tools to modulate astrocytic Ca 2+ signals have been of value in several studies in the field, showing that astrocyte function and astrocyte-neuron communication is heavily impacted during pathological conditions (Nedergaard et al, 2010;Nanclares et al, 2021;Herrera Moro Chao et al, 2022). Visualization of astrocyte Ca 2+ by GECIs monitoring has shown that astrocytes become hyperactive in many neurological diseases such as traumatic brain injury, amyotrophic lateral sclerosis, epilepsy, and Alzheimer's disease (AD) (Shigetomi et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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Calcium signaling in astrocytes and gliotransmitter release

Goenaga

Araque

Kofuji

et al. 2023

Front. Synaptic Neurosci.

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Glia are as numerous in the brain as neurons and widely known to serve supportive roles such as structural scaffolding, extracellular ionic and neurotransmitter homeostasis, and metabolic support. However, over the past two decades, several lines of evidence indicate that astrocytes, which are a type of glia, play active roles in neural information processing. Astrocytes, although not electrically active, can exhibit a form of excitability by dynamic changes in intracellular calcium levels. They sense synaptic activity and release neuroactive substances, named gliotransmitters, that modulate neuronal activity and synaptic transmission in several brain areas, thus impacting animal behavior. This “dialogue” between astrocytes and neurons is embodied in the concept of the tripartite synapse that includes astrocytes as integral elements of synaptic function. Here, we review the recent work and discuss how astrocytes via calcium-mediated excitability modulate synaptic information processing at various spatial and time scales.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Calcium signaling in astrocytes and gliotransmitter release

Goenaga

Araque

Kofuji

et al. 2023

Front. Synaptic Neurosci.

Self Cite

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“…Hypothalamic inflammation and gliosis are thought to be the foundation of hypothalamic circuit dysfunction, which can result in metabolic disorders like obesity [ 39 ]. Maternal high-fat diets (HFD) lead to lipid deposition and extensive proinflammatory gene expression in uterus.…”

Section: The Impact Of Maternal Obesity On the Hypothalamus Of The Of...mentioning

confidence: 99%

“…It activated inflammatory signaling pathways in astrocytes and triggered the release of inflammatory cytokines such as IL-6, which enhanced the proliferation of astrocytes in fetal hypothalamus [ 38 , 48 , 52 ]. In the PVH, proliferating astrocytes alter the activity of neighboring neurons, thereby changing the energy balance and peripheral glucose metabolism [ 39 ]. Activated astrocytes also produced and released transforming growth factor-β (TGF-β).…”

Section: The Impact Of Maternal Obesity On the Hypothalamus Of The Of...mentioning

confidence: 99%

Emerging role of hypothalamus in the metabolic regulation in the offspring of maternal obesity

Zhang

et al. 2023

Front. Nutr.

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Maternal obesity has a significant impact on the metabolism of offspring both in childhood and adulthood. The metabolic regulation of offspring is influenced by the intrauterine metabolic programming induced by maternal obesity. Nevertheless, the precise mechanisms remain unclear. The hypothalamus is the primary target of metabolic programming and the principal regulatory center of energy metabolism. Accumulating evidence has indicated the crucial role of hypothalamic regulation in the metabolism of offspring exposed to maternal obesity. This article reviews the development of hypothalamus, the role of the hypothalamic regulations in energy homeostasis, possible mechanisms underlying the developmental programming of energy metabolism in offspring, and the potential therapeutic approaches for preventing metabolic diseases later in life. Lastly, we discuss the challenges and future directions of hypothalamic regulation in the metabolism of children born to obese mothers.

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“…Like pancreatic b-cells, these neurons are specialized to sense glucose. In addition, tanycytes, astrocytes, and other glial cells implicated in glucose homeostasis are concentrated in this brain area (43,(45)(46)(47)(48).…”

Section: The Blood Glucose-sensing Modelmentioning

confidence: 99%

Brain Glucose Sensing and the Problem of Relative Hypoglycemia

et al. 2023

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“Relative hypoglycemia” is an often-overlooked complication of diabetes characterized by an increase in the glycemic threshold for detecting and responding to hypoglycemia. The clinical relevance of this problem is linked to growing evidence that among patients with critical illness, higher blood glucose in the intensive care unit is associated with higher mortality among patients without diabetes but lower mortality in patients with preexisting diabetes and an elevated prehospitalization HbA1c. Although additional studies are needed, the cardiovascular stress associated with hypoglycemia perception, which can occur at normal or even elevated glucose levels in patients with diabetes, offers a plausible explanation for this difference in outcomes. Little is known, however, regarding how hypoglycemia is normally detected by the brain, much less how relative hypoglycemia develops in patients with diabetes. In this article, we explore the role in hypoglycemia detection played by glucose-responsive sensory neurons supplying peripheral vascular beds and/or circumventricular organs. These observations support a model wherein relative hypoglycemia results from diabetes-associated impairment of this neuronal glucose-sensing process. By raising the glycemic threshold for hypoglycemia perception, this impairment may contribute to the increased mortality risk associated with standard glycemic management of critically ill patients with diabetes.

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Hypothalamic astrocytes control systemic glucose metabolism and energy balance

Cited by 45 publications

References 74 publications

Calcium signaling in astrocytes and gliotransmitter release

Calcium signaling in astrocytes and gliotransmitter release

Emerging role of hypothalamus in the metabolic regulation in the offspring of maternal obesity

Brain Glucose Sensing and the Problem of Relative Hypoglycemia

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