![]() Lastly, the response to fasting is sustained during a 2-day period and reversed by refeeding. ![]() Furthermore, a number of genes are induced by fasting in a BMAL1-dependent manner, so the clock modulates part of the fasting response. Also, specific classes of genes are temporally regulated by the clock and distinct fasting-sensitive TFs. Fasting attenuates the rhythmicity of brain and muscle Arnt-like protein-1 (BMAL1) post-translational modification and REV-ERBα levels both in liver and skeletal muscle, leading to repression and derepression of their target genes, respectively. We show that fasting affects daily rhythmic physiology by inducing various de novo oscillatory genes, which are distinct from those responsive to timed-feeding regimens. Moreover, food restriction confers robustness to circadian rhythms, possibly mediating the protective effects of fasting against diverse diseases and aging ( Hatori et al., 2012).Īlthough several studies have linked fasting to circadian rhythms ( Kawamoto et al., 2006 Shavlakadze et al., 2013 Sun et al., 2015 Xie et al., 2016), it is still unclear how fasting impinges on the clock and fasting-induced TFs. Recent studies suggest that a fasting-mimicking diet and temporal feeding restriction have numerous health benefits, despite comparable calorie intake ( Brandhorst et al., 2015 Hatori et al., 2012). Such metabolic shifts across different tissues are achieved by fasting-induced transcription factors (TFs) such as glucocorticoid receptor (GR), cyclic AMP responsive element binding protein (CREB), forkhead box TF class O (FOXO), TFEB, and peroxisome proliferator-activated receptors (PPARs) ( Goldstein and Hager, 2015). In parallel, the liver performs ketogenesis to supply ketone bodies to other vital organs, including the brain, by harnessing free fatty acids from adipose tissue ( Longo and Mattson, 2014). Skeletal muscles undergo protein breakdown and provide amino acids for the liver to implement gluconeogenesis, producing glucose to maintain appropriate blood glucose levels. In mammals, a drastic shift in metabolism takes place under low nutrient availability. Finally, while evidence on how food intake is integrated into circadian transcriptional regulation is accumulating ( Asher and Sassone-Corsi, 2015), how lack of food operates on the clock remains virtually unexplored.įasting is an adaptive state of metabolism when exogenous nutrient intake is limited ( Longo and Mattson, 2014). ![]() Although the circadian clock plays an important role in rhythmic gene expression, time-restricted feeding restores cyclic gene expression in arrhythmic Cry1 - /-, Cry2 - /- mutant mice, suggesting that nutrient-responsive transcriptional pathways contribute to the rhythmicity of circadian genes in a clock-independent manner ( Vollmers et al., 2009). Also, the clock regulates metabolic genes in a tissue-specific fashion, emphasizing the link between the circadian clock and metabolism ( Dyar et al., 2013 Nakahata et al., 2009 Ramsey et al., 2009 Zhang et al., 2015). The master pacemaker within the suprachiasmatic nucleus (SCN) is reset by light, while peripheral oscillators can be uncoupled from the SCN through food intake, highlighting the significance of temporal nutrient availability ( Asher and Sassone-Corsi, 2015 Damiola et al., 2000 Stokkan et al., 2001).ĭietary regimens and time-restricted feeding have a profound impact on the clock in metabolic tissues ( Eckel-Mahan et al., 2013 Hatori et al., 2012 Kohsaka et al., 2007 Mukherji et al., 2015 Tognini et al., 2017 Vollmers et al., 2009). The mammalian circadian clock consists of a molecular machinery that operates in all cells and is fine-tuned by environmental cues to generate 24-hr rhythms in metabolism, physiology, and behavior ( Bass and Takahashi, 2010 Schibler and Sassone-Corsi, 2002). Thus, fasting imposes specialized dynamics of transcriptional coordination between the clock and nutrient-sensitive pathways, thereby achieving a switch to fasting-specific temporal gene regulation. Third, the rhythmic genomic response to fasting is sustainable by prolonged fasting and reversible by refeeding. Second, fasting induces a switch in temporal gene expression through dedicated fasting-sensitive transcription factors such as GR, CREB, FOXO, TFEB, and PPARs. First, fasting affects core clock genes and proteins, resulting in blunted rhythmicity of BMAL1 and REV-ERBα both in liver and skeletal muscle. We demonstrate that the transcriptional response to fasting operates through molecular mechanisms that are distinct from time-restricted feeding regimens. While food is a known zeitgeber for clocks in peripheral tissues, it remains unclear how lack of food influences clock function. The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |