Insulin and leptin oscillations license food-entrained browning and metabolic flexibility [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101116 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28711500_1.fastq.gz | Fastqsanger.gz | |||
| SRR28711500_2.fastq.gz | Fastqsanger.gz | |||
| SRR28711501_1.fastq.gz | Fastqsanger.gz | |||
| SRR28711501_2.fastq.gz | Fastqsanger.gz | |||
| SRR28711502_1.fastq.gz | Fastqsanger.gz |
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Project description:Insulin and leptin oscillations license food-entrained browning and metabolic flexibility
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Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
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Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
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Project description:Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.
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