Activation of the Crtc2/Creb1 transcriptional network in skeletal muscle enhances weight loss during intermittent fasting
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA627469 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Exercise is a behavior modification indispensable for long-term weight loss. Exercise activates the Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators to drive Creb1-mediated anabolic transcriptional programs in skeletal muscle. Here, we show that induced overexpression of a skeletal muscle specific Crtc2 transgene in aged mice leads to greater weight loss during alternate day fasting, and selective loss of fat rather than lean mass. Transcriptional profiling revealed that fasting and weight loss downregulated most of the mitochondrial electron transport genes and other regulators of mitochondrial function that were substantially reversed in the Crtc2 mice, which maintained higher energy expenditure during fasting. The Crtc2 mice displayed greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity before the fast, suggesting muscle-intrinsic mechanisms in support of improved weight loss. This work reveals that Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb contribute to the effects of exercise on metabolism and weight loss.
2021-11-09 | GSE149150 | GEO
Project description:This study describes the effects of intermittent fasting induced weight loss on metabolic and molecular pathways
2023-07-01 | GSE196335 | GEO
Project description:Various intermittent fasting regimes are popularly being practiced but the scientific understanding for the mechanisms of intermittent fasting remains unclear. Observing the overall transcriptomic changes in specific organs, including heart, may contribute substantially in understanding the diverse effects of intermittent fasting. Our current study further investigate the differential transcriptomic changes in the heart among the different regimes of intermittent fasting as well.
2023-09-27 | GSE133290 | GEO
Project description:Transcription factors may orchestrate the health benefits of intermittent fasting through directing the expression of genome. Here, we find intermittent fasting can spin the spatiotemporal profile of transcription factors, and provide an atlas of transcription factors in biological space, time and feeding regimen.
2022-10-27 | GSE154797 | GEO
Project description:To better understand the hepatic metabolic response to intermittent fasting in chickens, Red Junglefowl chickens were raised on ad libitum (AL) feed until 14 days of age and then kept on AL feeding, switched to chronic feed restriction (CR) to around 70% or switched to an intermittent fasting (IF) regimen consisting of two fed days (150% of age-matched weight-specific AL intake offered daily) followed by a non-fed day. AL and CR were culled at 36 days of age, and IF birds either at 40 days of age (second consecutive feeding day) or 41 days of age (fasting day).
2022-04-14 | E-MTAB-7829 | biostudies-arrayexpress
Project description:Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners.
2018-07-11 | GSE116878 | GEO
Project description:In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.
2024-01-16 | PXD041351 | Pride
Project description:In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.
2024-01-16 | GSE229690 | GEO
Project description:Intermittent fasting (IF) increases lifespan, decreases metabolic disease phenotypes, and cancer risk in model organisms, but the mechanisms mediating these effects are not fully characterized. In particular, the altered transcriptional programming has yet to be defined in key fasting responsive tissues such as liver from animals undergoing intermittent fasting. In this study, we employed every-other-day-fasting (EODF) in mice and high-resolution proteome analysis of liver and blood plasma as a screening tool to identify key regulated pathways with comparison to ad libitum fed animals. We observed many changes in the liver proteome abundance profile that were distinct from those observed after a single bout of fasting. Key among these were the induction by EODF of de novo lipogenesis (DNL) and cholesterol biosynthesis pathway enzymes, which were mirrored by related metabolite changes such as increased triacylglycerides and HMG-CoA in EODF liver of fed mice. Paradoxically, we also observed the up-regulation of mitochondrial proteins associated with fatty-acid beta oxidation including ACOT2, which is known to accelerate this pathway in vivo. The most surprising observation was the EODF-mediated 16-fold down-regulation of alpha-1-antitrypsin (SERPINA1E) in liver, which is an abundant plasma protein made exclusively in this tissue. Plasma proteome analysis confirmed a 3-fold decrease in SERPINA1E after 2 weeks of EODF among other significant changes such as increased levels of APOA4, a finding in common with previous human EODF intervention studies. We determined that in liver the SREBP1c and HNF4A transcription factors were playing a major role in the up-regulation of lipid/cholesterol synthesis and down-regulation of AAT, respectively. Further characterization of HNF4A function suggested a global inhibition of its ability to bind promoters of target genes in livers from EODF animals, which we hypothesize is mediated by either increased linoleic acid binding, or post translational modifications of HNF4A protein in EODF animal liver tissue. Together these data provide a comprehensive Omics resource highlighting the key changes observed during the intermittent fasting response in a model animal.
2020-04-30 | PXD015553 | Pride
Project description:Evolutionary considerations suggest that the body has been optimized to perform at a high level in the fasted state when fatty acids and their ketone metabolites are a major fuel source for muscle cells. Because fasting is the most potent physiological stimulus for ketosis, we designed a study to determine the impact of intermittent fasting during endurance training on performance, and to elucidate the underlying cellular and molecular mechanisms. Male mice were randomly assigned to either ad libitum feeding or alternate-day fasting (AF) groups, and half of the mice in each diet group were trained daily on a treadmill for 1 month (45 minutes of running with increasing speed or incline each week). A run to exhaustion endurance test performed at the end of the training period revealed superior performance in the mice maintained on AF during training compared to mice fed ad libitum during training. VO2max was increased similarly by treadmill training in mice on AF or ad libitum diets, whereas respiratory exchange ratio (RER) was reduced in AF mice on fasting days and during running. Analyses of gene expression in liver and soleus tissues, and metabolomics analysis of blood suggest that the metabolic switch invoked by AF and potentiated by exercise strongly modulate molecular pathways involved in mitochondrial biogenesis, metabolism and cellular plasticity. Our findings demonstrate intermittent fasting engages metabolic and cellular signaling pathways that result in increased metabolic efficiency and endurance capacity.
2018-09-10 | GSE104079 | GEO