Biology subjects

Okun, E.

Publications and source records attributed to Okun, E..

4 recordsLinked to original sources

bioRxiv2025

Uncovering Shared and Tissue-Specific Molecular Adaptations to Intermittent Fasting in Liver, Brain, and Muscle

Intermittent fasting (IF) has emerged as a powerful dietary intervention with profound metabolic benefits, yet the tissue-specific molecular mechanisms underlying these effects remain poorly understood. In this study, we employed comprehensive proteomics and transcriptomics analysis to investigate the systemic and organ-specific adaptations to IF in male C57BL/6 mice. Following a 16-hour daily fasting regimen (IF16) over four months, IF reduced blood glucose, HbA1c, and cholesterol levels while increasing ketone bodies, indicative of enhanced metabolic flexibility. Proteomic profiling of the liver, skeletal muscle, and cerebral cortex revealed tissue-specific responses, with the liver exhibiting the most pronounced changes, including upregulation of pathways involved in fatty acid oxidation, ketogenesis, and glycan degradation, and downregulation of steroid hormone and cholesterol metabolism. In muscle, IF enhanced pyruvate metabolism, fatty acid biosynthesis, and AMPK signaling, while suppressing oxidative phosphorylation and thermogenesis. The cerebral cortex displayed unique adaptations, with upregulation of autophagy, PPAR signaling, and metabolic pathways, and downregulation of TGF-beta and p53 signaling, suggesting a shift toward energy conservation and stress resilience. Notably, Serpin A1c emerged as the only protein commonly upregulated across all three tissues, highlighting its potential role in systemic adaptation to IF. Integrative transcriptomic and proteomic analyses revealed partial concordance between mRNA and protein expression, underscoring the complexity of post-transcriptional regulation. Shared biological signaling processes were identified across tissues, suggesting unifying mechanisms linking metabolic changes to cellular communication. Our findings reveal both conserved and tissue-specific responses by which IF may optimize energy utilization, enhance metabolic flexibility, and promote cellular resilience.

molecular biology↗

bioRxiv2025

Intermittent Fasting Reprograms Chromatin Accessibility to Modulate Gene Expression in Brain and Muscle

Intermittent fasting (IF), a dietary regimen that mimics the natural feeding patterns observed across diverse organisms--from single-celled life to mammals--is thought to activate systemic survival responses and confer health benefits. However, the molecular mechanisms underlying these effects remain poorly understood. In this study, we utilized ATAC-Seq and RNA-Seq to investigate how IF influences chromatin accessibility and gene expression in brain and muscle tissues of mice, compared to ad libitum feeding. Our results reveal that IF induces significant changes in chromatin accessibility, modulating pathways related to metabolism, ribosome function, HIF-1 signaling, and glycolysis. Motif analysis identified tissue-specific transcription factors enriched in IF-regulated regions, including Sp1, Mef2a, NeuroD2, Banp, and NFIA in the brain, and SMAD4, TCF4, STAT5B, NKX3-1, and ZEB2 in muscle. Integrative analysis of ATAC-Seq and RNA-Seq data demonstrated that IF upregulates 50 genes and downregulates 15 in the cortex, while upregulating 31 genes and downregulating 10 in muscle. These gene expression changes are linked to pathways associated with neuroprotection and enhanced muscle function, offering mechanistic insights into the health benefits of IF. Our findings underscore the role of IF-induced chromatin remodeling in driving adaptive gene regulation.

bioinformatics↗

bioRxiv2020

Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis

Down Syndrome (DS) features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Amyloid-{beta} (A{beta}) overproduction and tau hyper-phosphorylation. As DS can be diagnosed in utero, maternally transferred anti-A{beta} antibodies might promote removal of early accumulation of A{beta} from the CNS. A DNA-vaccine expressing A{beta}1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early A{beta} plaque formation, similar to individuals with DS. Maternal A{beta}-specific antibodies provided transgenic offspring with passive immunization against A{beta} via the placental and subsequently lactation. Maternal antibodies reduced cortical A{beta} levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits and activation of the Fc{gamma}R1/Syk/Cofilin pathway in microglia. Sera from immunized dams facilitated A{beta} clearance by microglia in a Syk-dependent manner. These data suggest that maternal anti-A{beta} immunization is a potential strategy to alleviate cognitive decline in individuals with DS.

neuroscience↗

bioRxiv2020

Integrative Epigenomic and Transcriptomic Analysis Reveals Robust Metabolic Switching in the Brain During Intermittent Fasting

Intermittent fasting (IF) is a lifestyle intervention comprising a dietary regimen in which energy intake is restricted via alternating periods of fasting and ad libitum food consumption, without compromising nutritional composition. While epigenetic modifications can mediate effects of environmental factors on gene expression, no information is yet available on potential effects of IF on the epigenome. In this study, we found that IF causes modulation of histone H3 lysine 9 trimethylation (H3K9me3) epigenetic mark in the cerebellum of male C57/BL6 mice, which in turn orchestrates a plethora of transcriptomic changes involved in the robust metabolic switching processes commonly observed during IF. Interestingly, both epigenomic and transcriptomic modulation continued to be observed after refeeding, suggesting that memory of the IF-induced epigenetic change is maintained at the locus. Notably though, we found that termination of IF results in a loss of H3K9me3 regulation of the transcriptome. Collectively, our study characterizes a novel mechanism of IF in the epigenetic-transcriptomic axis, which controls myriad metabolic process changes. In addition to providing a valuable and innovative resource, our systemic analyses reveal molecular framework for understanding how IF impacts the metaboloepigenetics axis of the brain. Highlights{circ} Intermittent fasting (IF) and refeeding modifies epigenome in the cerebellum {circ}Integrative epigenomic and transcriptomic analyses revealed metabolic switching {circ}IF affects the metaboloepigenetics axis in regulating metabolic processes {circ}Integrative analyses revealed a loss of epigenetic reprogramme following refeeding

neuroscience↗