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High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila II

ABSTRACT: High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila II

PROVIDER: PRJNA531918 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8878040.fastq.gz	Fastqsanger.gz
	SRR8878041.fastq.gz	Fastqsanger.gz
	SRR8878042.fastq.gz	Fastqsanger.gz
	SRR8878043.fastq.gz	Fastqsanger.gz
	SRR8878044.fastq.gz	Fastqsanger.gz

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High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila I

Project description:High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila I

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High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila II

Project description:The function of the central nervous system to regulate food intake can be disrupted by sustained metabolic challenges such as high-fat diet (HFD), which may contribute to the development of various metabolic disorders. In the present study, we found that HFD specifically enhanced food-seeking behavior in fruit flies without altering flies’ baseline metabolism and food consumption. Mechanistically, HFD increased the excitability of a small group of octopaminergic (OA) neurons to a hunger hormone named adipokinetic hormone (AKH), via increasing the accumulation of AKH receptor (AKHR) in these neurons. Upon HFD, excess dietary lipids are transported by a lipoprotein LTP to enter these OA+AKHR+ neurons via the cognate receptor LpR1, which in turn activated AMPK-TOR signaling and suppressed autophagy-dependent degradation of AKHR. Taken together, we uncovered a mechanism that linked HFD, AMPK-TOR signaling, neuronal autophagy, and food-seeking behavior, providing insight in the reshaping of neural circuitry under metabolic challenges and the progression of metabolic diseases.

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Project description:Considering the distinct physiologies of men and women, it stands to reason that they would react differently to solar exposure, but such a study was never conducted before. Here we show that solar exposure induces food-seeking behavior, food intake and weight gain in males, but not in females, by epidemiological analysis, blood-serum proteomics, UVB-exposed mouse behavioral models and human cohort questionnaires . The underlying mechanism entails increased ghrelin secretion from skin adipocytes into the circulation. UVB irradiation led to p53 transcriptional activation of ghrelin in skin adipocytes, with mouse conditional p53-knockout abolishing UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53–chromatin interaction on the ghrelin promotor, thus blocking ghrelin and, consequently, food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of human physiology in furless animals and may lead to therapeutic opportunities for sex-based treatment of endocrine-related diseases.

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Coordination of hunger and sleep through circadian regulation of transcription in energy-sensing neurons

Project description:Alignment of fasting and feeding with the sleep/wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through transcription pathway maximizes eating during autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Synaptic and circadian pathways were specific to whole cell RNA analyses, while bioenergetic pathways were selectively enriched in the ribosome-bound transcriptome. Finally, we demonstrate that the AgRP clock mediates the transcriptional food acquisition with sleep/wake state. response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with sleep/wake state.

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microRNA regulation related to the protective effects of environmental enrichment against cocaine-seeking behavior

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