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Leptin responsive neurons

ABSTRACT: Leptin responsive neurons

PROVIDER: PRJNA439388 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6873610.fastq.gz	Fastqsanger.gz
	SRR6873620.fastq.gz	Fastqsanger.gz
	SRR6873630.fastq.gz	Fastqsanger.gz
	SRR6873640.fastq.gz	Fastqsanger.gz
	SRR6873650.fastq.gz	Fastqsanger.gz

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Leptin responsive neurons

Project description:Genome wide association studies (GWAS) in obesity have identified a large number of noncoding loci located near genes expressed in the central nervous system. However, due to the difficulties in isolating and characterizing specific neuronal subpopulations, very few obesity-associated SNPs have been functionally characterized. Leptin responsive neurons in the hypothalamus are essential in controlling energy homeostasis and body weight. Here, we show that by combining FACS-sorting of leptin-responsive hypothalamic neuron nuclei with genomic approaches (RNA-seq, ChIP-seq, ATAC-seq), we can provide a comprehensive map of leptin-response specific regulatory elements, several of which overlap obesity-associated GWAS variants. Further demonstrating the robustness of our leptin-response neuron regulome, we functionally characterize a novel enhancer near Socs3, a leptin response-associated transcription factor. Combined, our results provide a comprehensive map of active genomic regions in leptin-responsive neurons and present a blueprint for functionally characterizing obesity-associated SNPs in the hypothalamus.

2019-04-01 | GSE112125 | GEO

Leptin-responsive dorsomedial hypothalamic neurons link circadian and metabolic systems to govern food anticipation [snRNA-seq]

Project description:In contrast to light-dependent entrainment of the central circadian pacemaker, the molecular and neural underpinnings of entrainment by non-photic cues, such as food, remain unclear. Using single-nucleus RNA-sequencing, we identified a leptin receptor (LepR) positive neuronal population in the dorsomedial hypothalamus (DMH) that is responsive to scheduled feeding (SF). During SF, DMH LepR neuron activity precedes an impending meal. Mis-timed exogenous leptin administration or chemogenetic activation of DMH LepR neurons inhibits both neuronal and behavioral food anticipatory activities. Further, repetitive chemogenetic activation of DMH LepR neurons partitions a secondary bout of circadian locomotor activity in phase with the stimulation. This work places DMH LepR neurons as an essential integrator of food entrainment, and positions leptin as a critical central mediator of this circadian response.

2023-06-14 | GSE211757 | GEO

Transcriptomic Changes in Adult Hypothalamic Neurons Following Leptin Sensitivity Modulation

Project description:Modulating leptin sensitivity in hypothalamic neurons is critical for metabolic regulation and plays a key role in the development of obesity. This study examines the effects of three distinct approaches—leptin exposure (LEPA), leptin antagonist administration (LANTA), and palmitate treatment (PA)—on adult-derived mHypoA-2/12 neurons. Transcriptomic analysis using 3' mRNA-Seq revealed significant downregulation of several pathways, including the NOD-like receptor signaling pathway, C-type lectin receptor signaling pathway, NF-κB signaling pathway, and IL-17 signaling pathway. These pathways are closely linked to neuroinflammatory processes, suggesting that modulating leptin sensitivity may influence inflammation in the hypothalamus. The observed downregulation indicates a complex interaction between leptin signaling and cellular stress responses, which may represent an adaptive mechanism to prolonged exposure to leptin or fatty acids. Understanding these dynamics is crucial for gaining insight into how neuroinflammation contributes to the development of leptin resistance and related metabolic disorders.

2024-11-22 | GSE280030 | GEO

Leptin-responsive dorsomedial hypothalamic neurons link circadian and metabolic systems to govern food anticipation [snRNA-seq]

Project description:Leptin-responsive dorsomedial hypothalamic neurons link circadian and metabolic systems to govern food anticipation [snRNA-seq]

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Defining the Transcriptional Targets of Leptin Reveals a Role for Atf3 in Leptin Action

Project description:We employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient (Lepob/ob) mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor Atf3 in LepRb neurons.

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Transciption profiling of leptin receptor-expressing neurons in the Nucleus of the Solitary Tract

Project description:This study aims to identify and compare unique transcription profiles of neurons in the NTS that express the leptin receptor. We conducted single-cell patch RNA-sequencing experiments to classify neurons first by their unique firing properties and, second, transciptional profiles. We found two unique cellular populations: type1 and type2 distinguishable by firing patterns and transciption profile.

2020-12-07 | GSE158582 | GEO

KCNB1-Leptin receptor complexes couple electric and endocrine function in the melanocortin neurons of the hypothalamus

Project description:The neurons of the melanocortin system regulate feeding and energy homeostasis through a combination of electrical and endocrine mechanisms. However, the molecular basis for this functional heterogeneity are poorly understood. Here, a voltage-gated potassium (K+) channel named KCNB1 (alias Kv2.1), formed stable complexes with the leptin receptor (LepR) in proopiomelanocortin (POMC) expressing neurons of the Arcuate nucleus of the hypothalamus (ARCPOMC). Mice lacking functional KCNB1 channels (NULL mice), exhibited constitutive depolarization of ARCPOMC neurons along with aberrant POMC production. In NULL neurons, canonical LepR-STAT3 signaling--which underlies POMC production--was impaired, whereas non-canonical insulin receptor substrate PI3K/Akt/FOXO1 and ERK signaling were significantly upregulated. Accordingly, the NULL animals were insensitive to anorexic stimuli induced by leptin administration and produced less adipose tissue and circulating leptin than WT animals. Taken together, these findings unveil an exquisite mechanism of metabolic regulation whereby synergistic control of neuronal excitability and endocrine function is achieved through the partnership between a K+ channel and a hormone receptor. As aberrant KCNB1 channels cause developmental and epileptic encephalopathies, these results further establish a K+ channel as a causative link between epileptic and metabolic disorders.

2024-11-20 | GSE246918 | GEO

Morphine-responsive neurons that regulate mechanical antinociception

Project description:Morphine-responsive neurons that regulate mechanical antinociception

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Transcriptomic Changes in Adult Hypothalamic Neurons Following Leptin Sensitivity Modulation

Project description:Transcriptomic Changes in Adult Hypothalamic Neurons Following Leptin Sensitivity Modulation

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Expression data from leptin administration to Lepob/Lepob mice and Lepmkyo/Lepmkyo rats

Project description:Leptin-responsive genes in the pathway of a leptin signal from the hypothalamus to the liver has not been detected. We used microarray to detailed the expression of gene in liver in the status of leptin deficiency, and leptin administration. As leptin deficient status, we use Lepmkyo/Lepmkyo rats or Lepob/Lepob mice and their wild type littermates.

2012-11-28 | GSE42532 | GEO

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