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Regulatory T-cells in the hypothalamus control immune activation and improve metabolic impairments upon high-calorie environments

ABSTRACT: Regulatory T-cells in the hypothalamus control immune activation and improve metabolic impairments upon high-calorie environments

PROVIDER: PRJNA1186813 | ENA |

REPOSITORIES: ENA

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Regulatory T-cells in the hypothalamus control immune activation and improve metabolic impairments upon high-calorie environments

Project description:The hypothalamus in the central nervous system (CNS) plays a key role in the control of systemic metabolism. A calorie-rich diet triggers CNS immune activation, which contributes to impairments of metabolic control, favoring obesity and Type 2 Diabetes (T2D). However, cell types and molecular processes regulating hypothalamic immune activation remain incompletely understood. Here, we report the functionally relevant presence of regulatory T cells (Tregs), key players in the control of immune and tissue homeostasis, in the hypothalamus. Exposure to calorie-rich environments triggers immune activation of hypothalamic CD4+T cells, infiltrating macrophages and microglia while decreasing the presence of hypothalamic Tregs in mice. mRNA expression profiling of hypothalamic CD4+T cells revealed a Th1-like activation state evidenced by high levels of Tbx21, Cxcr3 and Cd226 and a decrease of Ccr7 and S1pr1 expression, a profile typical for recruitment of T cells to and retention at inflammatory sites. Importantly, mechanistic Treg loss- and gain-of-function experiments in vivo, show that Foxp3+Tregs limit hypothalamic immune activation and improve metabolic impairments induced by hyper-caloric feeding. Our findings refine the current model of immuno-metabolic crosstalk in the brain in response to environmental challenges and are of relevance for the future development of immune interventions to support health in obesity and T2D.

2025-01-20 | GSE282067 | GEO

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior and hypothalamic gene expression

Project description:Caloric restriction is a robust intervention to increase life span. Giving less food (CR), or allowing free access to diluted diet with indigestible components (CD) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compared responses of C57BL/6 mice to equivalent levels of CR and CD. Our study calorie restriction and calorie two restriction methods different effect on hypothamic gene expression pattern, RNA-seq was performed using hypothalamus of mice with 2 methods treatment as well as control group.

2022-05-17 | GSE200820 | GEO

Genome-wide profiling of hypothalamus, cerebellum, striatum, and frontal cortex across young, middle-aged, and aged mice

Project description:We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex

2016-09-20 | GSE87102 | GEO

Comparison between calorie-restricted and time-restricted without calorie restriction

Project description:Comparison between calorie-restricted and time-restricted without calorie restriction

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Calorie restriction and aging

Project description:Gene expression profiles of kidney tissue from control-fed 5-month-old, control-fed 30-month-old and calorie restricted 30 month-old C57BL/6 mice. Keywords = kidney, aging, calorie restriction Keywords: other

2003-06-23 | GSE459 | GEO

Human hypothalamus

Project description:Human hypothalamus

| PRJNA688901 | ENA

Foxp3+ regulatory T cells control hypothalamic inflammation

Project description:The central nervous system (CNS) hypothalamus controls systemic metabolism. Inflammatory CNS processes evolving upon exposure to calorie-rich diet are thought to promote impaired metabolic CNS control, thereby triggering obesity and Type-2 diabetes (T2D). However, immune cells relevant for maintaining hypothalamic integrity remain incompletely understood. Here, we identify hypothalamic CD4+Foxp3+regulatory T(Treg) cells which control local tissue-inflammation. Specifically, upon exposure to a calorie-rich diet, a significant decline in hypothalamus-residing Foxp3+Tregs occurred and was accompanied by increased immune activation of CD4+T cells, infiltrating macrophages and microglia. Microglial proteomes of mice exposed to the hypercaloric challenge confirmed characteristics of immune activation; specifically, mRNA expression profiling of hypothalamic CD4+T cells indicated a Th1-mediated inflammatory state evidenced by high levels of Tbx21, Cxcr3, Cd226 and reduced expression of Ccr7 and S1P1 receptors relevant for recruitment to and retention at inflammatory sites. Using Treg depletion and transfer experiments in vivo, we found that Foxp3+Tregs critically limit hypothalamic immune activation induced by hyper-caloric challenge. Our findings open new avenues in the design of tailored concepts to improve immunometabolic health in obesity and T2D.

2025-01-20 | PXD004498 | Pride

Heterospermic pig hypothalamus

Project description:Hypothalamus heterospermic piglets

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Extreme environments

Project description:Extreme environments Raw sequence reads

| PRJNA885566 | ENA

Expression data for mouse hypothalamus

Project description:Strain differences in gene expression in the hypothalamus of BXD recombinant inbred mice We used microarrays to evaluate genetic and sex-specific differences in gene expression in the hypothalamus Hypothalamus was dissected from adult male and female mice and process for expression analysis

2012-03-22 | E-GEOD-36674 | biostudies-arrayexpress

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