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Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE153551 | GEO | 2020/07/01

REPOSITORIES: GEO

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Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission.

Project description: Not available

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Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [bulk RNA-seq]

Project description:In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the hypothalamus was recently identified as a key target for this effect. To investigate how FGF1 action in this brain area achieves this effect, we combined single-nucleeus RNA sequencing (RNA-seq) with single-cell and traditional RNA-seq to identify >70,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1, 5 and 42 after icv injection of either FGF1 or vehicle. In addition to robust transcriptomics effects on Agrp neurons, which persisted through Day 42, rapid inhibition of Agrp neurons by FGF1 was shown by both electrophysiology and cFos studies. This effect is predicted to increase hypothalamic melanocortin signaling, and we show that FGF1-induced diabetes remission is melanocortin-dependent, as it was prevented by either genetic or pharmacological blockade of central melanocortin receptors. Combined with dramatic transcriptional and morphological changes induced by icv FGF1 injection in tanycytes, astrocytes and oligodendrocytes, including increased cellular contacts between astrocytes and Agrp neurons, these findings implicate glial-neuron interactions as mediators of the sustained remission of diabetes induced by the hypothalamic action of FGF1 action.

2020-07-01 | GSE153549 | GEO

Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [single-cell RNA-seq]

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Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats.

Project description: Not available

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Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1

Project description:Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1

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Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [bulk RNA-seq]

Project description:Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [bulk RNA-seq]

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Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [single-cell RNA-seq]

Project description:Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [single-cell RNA-seq]

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Role of hypothalamic MAPK/ERK signaling in diabetes remission induced by the central action of fibroblast growth factor 1

Project description:The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes (T2D) following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that icv FGF1 injection induces signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family in the hypothalamus, and that this activation persists for at least 24h. Further, we show that in diabetic Lepob/ob mice, this prolonged response is required for the sustained antidiabetic action of FGF1, since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, elicits transient but not sustained glucose lowering. These data implicate sustained hypothalamic MAPK/ERK signaling in the mechanism underlying diabetes remission induced by icv FGF1.

2021-07-12 | GSE179918 | GEO

Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents.

Project description: Not available

| S-EPMC4938755 | biostudies-literature

Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors.

Project description: Not available

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