Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver

Ng, Gavin Yong-Quan; Kang, Seok Woo; Kim, Joonki; Alli-Shaik, Asfa; Baik, Sang‐Ha; Jo, Dong-Gyu; Hande, M. Prakash; Sobey, Christopher G.; Gunaratne, Jayantha; Fann, David Y.

doi:10.1177/1559325819876780

Cited by 21 publications

(21 citation statements)

References 34 publications

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“…S2). Among those, we found several GO terms consistent with previous fasting studies, including carboxylic acid biosynthetic process, lipid homeostasis, xenobiotic metabolism, regulation of protein stability, and regulation of protein localization to membrane [13,16,35]. Interestingly, we also identified other novel pathways enriched by STF, such as wound healing, sensory perception of pain and positive regulation of vasculature development, thus highlighting the discovery potential of this approach.…”

Section: Organ-specific Modulations By Stfsupporting

confidence: 85%

“…The advent of high-throughput omics facilitated the elucidation of some of the cellular and molecular mechanisms underlying the beneficial effects of fasting. Nonetheless, the majority of these studies focused on single organ response (i.e., the liver) and, less often, involved two or three organs [10][11][12][13][14][15][16]. The adaptation to energy deprivation, however, requires a multi-organ integration of metabolic modulations to protect the organism from an irreversible loss of resources [17].…”

Section: Introductionmentioning

confidence: 99%

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Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

Huang

Makhlouf

AbouMoussa

et al. 2020

Preprint

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Different fasting regiments are known to promote health, and chronic immunological disorders and mitigate age-related pathophysiological parameters in animals and humans. Indeed, several clinicals trials are currently ongoing using fasting as a potential therapy for a wide range of conditions. Fasting alters metabolism by acting as a reset for energy homeostasis, but the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are still not-well understood, particularly at a systems/multiorgan level. We investigated the dynamic gene expression patterns associated with periods of STF in nine different mouse organs. First, we identified both unique and shared transcriptional signatures at the organ and systemic levels. Second, we discovered differential temporal effects of STF among organs. Third, using gene ontology enrichment analysis, we identified an organ network, formed by the 63 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown, and perigonadal white adipose tissue, hence we name it the brain-liver-fats organ network. Fourth, we identified that the immune system, dominated by T cell regulation processes, is a central and prominent target of systemic modulations during short-term energy loss in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. In conclusion, our study provides a comprehensive multi-organ transcriptomic profiling of mice subjected to multiple periods of STF and added new insights into the molecular modulators involved in the systemic immuno-transcriptomic changes that occur during short-term energy loss.

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Section: Organ-specific Modulations By Stfsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

Huang

Makhlouf

AbouMoussa

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Activated AMPK induces a series of events resulting in reduced fatty acid synthesis, oxidation, and cholesterol synthesis, but active SIRT1 may increase ketogenesis and lipolysis, and decrease glycolysis. Other proteins can be involved in these processes [95].…”

Section: Epigenetic Link Between Nutrition Aging and Cancermentioning

confidence: 99%

“…Recently, Hernando-Herraez showed that mouse stem cells acquire epigenetic drift by the accumulation of stochastic changes of DNA methylation in the promoters of many genes, which leads to altered transcriptional control and the aging of stem cells [97]. Epigenetic mechanisms of anti-aging effects resulting from CR were then postulated and shown in several works [5,91,94,95,[98][99][100].…”

Section: Epigenetic Link Between Nutrition Aging and Cancermentioning

confidence: 99%

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

et al. 2020

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The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.

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“…Thus, it may counteract both ROS generation and effects [217,218]. Of note, it has been widely demonstrated that the beneficial effects of caloric restriction are also mediated by epigenetic mechanisms [219,220], that, as previously described, are tightly linked with the oxidative status of the cell.…”

Section: Antioxidants and Mitochondria: From The General Function To mentioning

confidence: 94%

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Bordoni

Gabbianelli

2020

Antioxidants

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The maintenance of the mitochondrial function is essential in preventing and counteracting neurodegeneration. In particular, mitochondria of neuronal cells play a pivotal role in sustaining the high energetic metabolism of these cells and are especially prone to oxidative damage. Since overproduction of reactive oxygen species (ROS) is involved in the pathogenesis of neurodegeneration, dietary antioxidants have been suggested to counteract the detrimental effects of ROS and to preserve the mitochondrial function, thus slowing the progression and limiting the extent of neuronal cell loss in neurodegenerative disorders. In addition to their role in the redox-system homeostasis, mitochondria are unique organelles in that they contain their own genome (mtDNA), which acts at the interface between environmental exposures and the molecular triggers of neurodegeneration. Indeed, it has been demonstrated that mtDNA (including both genetics and, from recent evidence, epigenetics) might play relevant roles in modulating the risk for neurodegenerative disorders. This mini-review describes the link between the mitochondrial genome and cellular oxidative status, with a particular focus on neurodegeneration; moreover, it provides an overview on potential beneficial effects of antioxidants in preserving mitochondrial functions through the protection of mtDNA.

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Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver

Cited by 21 publications

References 34 publications

Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

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