Time resolved and interorgan response of mice to systemic energetic starvation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE108299 | GEO | 2020/12/12
REPOSITORIES: GEO
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Project description:Time resolved and interorgan response of mice to systemic energetic starvation
| PRJNA423052 | ENA
Project description:The effects of fasting have been studied extensively, predominantly on isolated processes, within a specific organ. No comprehensive study of the adaptations was available for different organs, let alone interrelating them, which left the understanding of the body’s orchestration of fasting response limited. The gene expression profiles of brain, small intestine, kidney, liver and skeletal muscle were therefore studied in mice subjected to short, moderate and prolonged fasting. Functional category enrichment, network, and text-mining analyses were employed to scrutinize the overall adaptive response, aiming to identify responsive pathways, processes and networks, and their regulation. The implicated processes did not follow the accepted carbohydrate-lipid-protein succession of energy substrates expenditure. Instead, they were activated simultaneously in different organs during the whole duration of fasting. The most prominent changes occurred in lipid and steroid metabolism, especially in the liver and kidney, which showed biochemically similar, orchestrated responses. They were accompanied by suppression of the immune response and cell turnover, particularly in the small intestine, tied in with increased proteolysis in the muscle. Enhanced defence against oxidative damage, obvious in all the organs, was the top reaction of the brain, otherwise shown to be extremely well protected from starvation. The major transcription regulators of fasting response in different organs were FoxO transcription factors, AP-1, p53, cMyc, Sp1, EGF and HNF4α. The revealed interorgan interactions between metabolic, inflammatory and cell turnover responses are essential when designing strategies to treat the starvation affected individuals, while stressing the significance of using complimentary bioinformatics tools in the high-throughput data analysis. 6 week-old male FVB mice were fasted for 0, 12, 24, 48 or 72 hours before sacrifice (N = 5 per group). From each mouse total RNA was isolated from five organs - liver, small intestine, kidney, brain, and calf muscle. Five microarrays per experimental condition (five tissues, five timepoints) were performed. We used a common reference design. The single common-reference sample was a pool of equal amounts of RNA from all the samples investigated, including additional samples from 5 mice that were fasted for 48 hours and supplemented with vitamin B complex after 24 and 36 hours of fasting.
2011-03-09 | E-GEOD-24504 | biostudies-arrayexpress
Project description:The effects of fasting have been studied extensively, predominantly on isolated processes, within a specific organ. No comprehensive study of the adaptations was available for different organs, let alone interrelating them, which left the understanding of the body’s orchestration of fasting response limited. The gene expression profiles of brain, small intestine, kidney, liver and skeletal muscle were therefore studied in mice subjected to short, moderate and prolonged fasting. Functional category enrichment, network, and text-mining analyses were employed to scrutinize the overall adaptive response, aiming to identify responsive pathways, processes and networks, and their regulation. The implicated processes did not follow the accepted carbohydrate-lipid-protein succession of energy substrates expenditure. Instead, they were activated simultaneously in different organs during the whole duration of fasting. The most prominent changes occurred in lipid and steroid metabolism, especially in the liver and kidney, which showed biochemically similar, orchestrated responses. They were accompanied by suppression of the immune response and cell turnover, particularly in the small intestine, tied in with increased proteolysis in the muscle. Enhanced defence against oxidative damage, obvious in all the organs, was the top reaction of the brain, otherwise shown to be extremely well protected from starvation. The major transcription regulators of fasting response in different organs were FoxO transcription factors, AP-1, p53, cMyc, Sp1, EGF and HNF4α. The revealed interorgan interactions between metabolic, inflammatory and cell turnover responses are essential when designing strategies to treat the starvation affected individuals, while stressing the significance of using complimentary bioinformatics tools in the high-throughput data analysis.
2011-03-09 | GSE24504 | GEO
Project description:Pathenogenesis of atherosclerosis results from the interactions between disrupted lipid homeostasis and immune response, but the molecular bridges between the major players are still a matter of controversy. We performed a systemic study of the imflammatory cytokine tumor necrosis factor alpha (TNF alpha), a well established anorexia agent, in the livers of the mice exposed to 20h-cytokine/starvation. We show that treatment with TNF-alpha reverses adaptations to fasting. Moreover, it up-regulates cholesterol biosynthesis and down-regulates bile acids synthesis, which leads to disrupted cholesterol homeostasis and pro-atherogenic changes. Interestingly, we found that TNF alpha also interferes with gene regulation of the xenobiotic metabolism. Keywords: treatment and diet effects
2007-11-27 | GSE6423 | GEO
Project description:Pathenogenesis of atherosclerosis results from the interactions between disrupted lipid homeostasis and immune response, but the molecular bridges between the major players are still a matter of controversy. We performed a systemic study of the imflammatory cytokine tumor necrosis factor alpha (TNF alpha), a well established anorexia agent, in the livers of the mice exposed to 20h-cytokine/starvation. We show that treatment with TNF-alpha reverses adaptations to fasting. Moreover, it up-regulates cholesterol biosynthesis and down-regulates bile acids synthesis, which leads to disrupted cholesterol homeostasis and pro-atherogenic changes. Interestingly, we found that TNF alpha also interferes with gene regulation of the xenobiotic metabolism. Keywords: treatment and diet effects Mice have been either saline treated (nontreated group), saline treated and fasted for 20h (fasted group), and TNF-alpha treated (30 mikrograms per animal) and fasted for 20h (TNF-alpha group). 3 biological replicas from fasted and TNF-alpha groups were co-hybridized with pool of nontreated group. No dye-swaps were performed.
2010-05-25 | E-GEOD-6423 | biostudies-arrayexpress
Project description:Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.
| S-EPMC7998027 | biostudies-literature
Project description:Chromochloris zofingiensis has been proposed as a potential producer of lipids and the high-value carotenoid astaxanthin. Previous studies have demonstrated that TAG (triacylglycerol) and astaxanthin accumulated in a well-coordinated manner in response to different stresses in C. zofingiensis. The integrated production of lipids with co-products emerges as a new research direction and is proposed to be a promising approach toward offsetting the algal biodiesel production cost. Therefore, it is suggested C. zofingiensis can serve as research models for the integrated production. Sulfur starvation stress simultaneously induced TAG and astaxanthin accumulation in C. zofingiensis. To understand the mechanism underlying TAG and astaxanthin accumulation induced by sulfur starvation stress, we applied time-resolved high-throughput mRNA sequencing in C. zofingiensis.
2020-07-27 | GSE130454 | GEO
Project description:Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at Ser336 sustains mitochondrial fission and respiratory sufficiency. Timelapse imaging shows that NDRG1, but not phosphorylation-deficient NDRG1Ser336Ala mutant, engages with mitochondria to facilitate fission in both control and Drp1-deficient cells, reflecting independency from Drp1. Using proteomics, an siRNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase Cdc42 and effectors and regulators of Cdc42 to orchestrate fission. Accordingly, RictorKO, NDRG1Ser336Ala mutants, and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.
2023-04-27 | PXD041696 | Pride
Project description:The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. The results of this study demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demostrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation of their media, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. Taken together, these data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans.
2009-04-15 | GSE15656 | GEO
Project description:Mosquitoes that transmit many deadly infectious diseases also need to keep fighting against many microbial infections. Constitutive expression of multiple antimicrobial peptides (AMPs) in almost all body tissues is believed to facilitate the effective management of these local infections. When any infection breaches the local barrier, AMPs are induced rapidly in non-target tissues such as hemocytes (HCs) and establish their co-ordination with systemic immune effectors to clear off the body infection. But how interorgan immune communication is managed during local and systemic infections remain largely unknown. To understand this interorgan molecular relationship, we identified, extensively profiled and compared the expression of AMPs in three important mosquito tissues viz. midgut, fat body (FB), and HCs. dsRNA-mediated AMPs silencing suggests that mosquito tissues are able to manage an optimal expression of AMPs at the physiological level. We also examined the possible contribution of two important immune regulator genes relish (REL) and nitric oxide synthase, controlling AMPs expression in these tissues during local or systemic infections. We show that each tissue has a unique ability to respond to local/systemic challenges, but HCs are more specialized to recognize and discriminate-specific antigens than gut and FB. Our investigation also revealed that both REL and NO participate in the overall management of the interorgan immune responses, but at the same time each tissue also has its own ability to maintain the interorgan flow of signals. In our knowledge, this is the first large-scale study examining the interorgan immune relationship in the mosquito.
| S-EPMC5826171 | biostudies-literature