Feeding-Induced Discordance: Protein-mRNA Correlation Varies by Zone, Sex, and Fasting in Mouse Hepatocytes
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ABSTRACT:
PROVIDER: PRJNA1232797 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32599972_1.fastq.gz | Fastqsanger.gz | |||
| SRR32599972_2.fastq.gz | Fastqsanger.gz | |||
| SRR32599973_1.fastq.gz | Fastqsanger.gz | |||
| SRR32599973_2.fastq.gz | Fastqsanger.gz | |||
| SRR32599974_1.fastq.gz | Fastqsanger.gz |
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Project description:The mammalian liver plays an essential role in maintaining metabolic homeostasis in response to fasting and feeding. Additionally, the liver exhibits sex dimorphism and zonation. To investigate how these factors interact, we performed RNA-seq and proteomics on periportal and pericentral hepatocytes isolated from male and female mice under fed and starved conditions. We developed a classification system to assess protein-mRNA relationship and found that most zonation genes showed strong concordance between mRNA and protein. Classical growth hormone regulated sex-biased genes also exhibited concordance, while a significant subset of sex genes showed protein-level bias without corresponding mRNA differences. Transition between feeding and starvation triggered widespread changes in mRNA expression alongside rapid modulation of functional de novo lipogenesis. However, key lipogenic enzymes—such as ACC, ACLY, and FAS —showed little to no corresponding change at the protein level. To facilitate further exploration of these findings, we developed Discorda, a web-based database for interactive data analysis. Our findings reinforce the principle that mRNA changes do not reliably predict corresponding protein levels (and vice versa), particularly in the context of sex and acute metabolic regulation.
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Project description:The sensation of hunger after a period of fasting and the sensation of satiety after eating is crucial to behavioral regulation of food intake, but the biological mechanisms regulating these sensations are incompletely understood. We studied the behavioral and physiological adaptation to fasting in the vinegar fly (Drosophila melanogaster). Here we show that flies demonstrated increased behavioral attraction to food odor when food-deprived with no corresponding increase in sensitivity in the peripheral olfactory system. Flies increased their food intake transiently in the post-fasted state, but returned to a stable baseline feeding level within 24 hr after return to food. This modulation in feeding was accompanied by a significant increase in the size of the crop organ of the digestive system, suggesting that fasted flies responded both by increasing their food intake and storing reserve food in their crop. The post-fasting feeding response was observed in both male and female flies of diverse genetic backgrounds. Expression profiling of head, body, and chemosensory tissues by microarray analysis revealed several hundred genes that are regulated by feeding state, including 247 genes in the fly head. We performed RNA interference-mediated knockdown of, takeout, one of the genes strongly downregulated by fasting in multiple tissues. When takeout was knocked down in all neurons the post-fasting feeding response was abolished. These observations suggest that a coordinated transcriptional response to internal physiological state may regulate both ingestive behaviors and chemosensory perception of food 6 Pool of flies were used for this experiment. For each pool, samples were taken at 0,24 and 48h and separated in each body part. 56 samples were used for the analysis.
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Project description:The sensation of hunger after a period of fasting and the sensation of satiety after eating is crucial to behavioral regulation of food intake, but the biological mechanisms regulating these sensations are incompletely understood. We studied the behavioral and physiological adaptation to fasting in the vinegar fly (Drosophila melanogaster). Here we show that flies demonstrated increased behavioral attraction to food odor when food-deprived with no corresponding increase in sensitivity in the peripheral olfactory system. Flies increased their food intake transiently in the post-fasted state, but returned to a stable baseline feeding level within 24 hr after return to food. This modulation in feeding was accompanied by a significant increase in the size of the crop organ of the digestive system, suggesting that fasted flies responded both by increasing their food intake and storing reserve food in their crop. The post-fasting feeding response was observed in both male and female flies of diverse genetic backgrounds. Expression profiling of head, body, and chemosensory tissues by microarray analysis revealed several hundred genes that are regulated by feeding state, including 247 genes in the fly head. We performed RNA interference-mediated knockdown of, takeout, one of the genes strongly downregulated by fasting in multiple tissues. When takeout was knocked down in all neurons the post-fasting feeding response was abolished. These observations suggest that a coordinated transcriptional response to internal physiological state may regulate both ingestive behaviors and chemosensory perception of food
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