Abstract
BackgroundThe gut is the major organ for nutrient absorption and immune response in the body of animals. Although effects of fasting on the gut functions have been extensively studied in model animals (e.g. mice), little is known about the response of the gut to fasting in a natural condition (e.g. hibernation). During hibernation, animals endure the long term of fasting and hypothermia.ResultsHere we generated the first gut transcriptome in a wild hibernating bat (Rhinolophus ferrumequinum). We identified 1614 differentially expressed genes (DEGs) during four physiological states (Torpor, Arousal, Winter Active and Summer Active). Gene co-expression network analysis assigns 926 DEGs into six modules associated with Torpor and Arousal. Our results reveal that in response to the stress of luminal nutrient deficiency during hibernation, the gut helps to reduce food intake by overexpressing genes (e.g. CCK and GPR17) that regulate the sensitivity to insulin and leptin. At the same time, the gut contributes energy supply by overexpressing genes that increase capacity for ketogenesis (HMGCS2) and selective autophagy (TEX264). Furthermore, we identified separate sets of multiple DEGs upregulated in Torpor and Arousal whose functions are involved in innate immunity.ConclusionThis is the first gut transcriptome of a hibernating mammal. Our study identified candidate genes associated with regulation of food intake and enhance of innate immunity in the gut during hibernation. By comparing with previous studies, we found that two DEGs (CPE and HSPA8) were also significantly elevated during torpor in liver and brain of R. ferrumequinum and several DEGs (e.g. TXNIP and PDK1/4) were commonly upregulated during torpor in multiple tissues of different mammals. Our results support that shared expression changes may underlie the hibernation phenotype by most mammals.
Highlights
The gut is the major organ for nutrient absorption and immune response in the body of animals
After removing the overlapped differentially expressed genes (DEGs) identified in all six comparisons, a total of 1614 DEGs were retained (Fig. 2b, Table S5)
For upregulated DEGs, significant enrichments of Gene Ontology (GO) terms and/or KEGG and Reactome pathways were detected in Torpor, Winter Active and Arousal relative to other states (Figure S3, Table S6 and S7). We found that those DEGs upregulated in Torpor relative to Summer Active were associated with insulin-like Growth Factor (IGF), and those DEGs upregulated in Winter Active relative to Arousal were associated with carbohydrate metabolism (Figure S3 and Table S7)
Summary
The gut is the major organ for nutrient absorption and immune response in the body of animals. The gut is the major organ for food digestion and nutrient absorption in the body of animals. Studies about the effects of food deprivation and internal food stimuli on the gut have identified important genes, proteins, and molecules which modulate food intake (reviewed in [7], see [8]). Most of these studies focused on animals under daily food intake fluctuations. Studies on the effects of a prolonged fast on the gut function have been rarely conducted in a naturally occurring state, such as hibernation
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