Melatonin-mediated corrective changes in gut microbiota of experimentally chronodisrupted C57BL/6J mice.

Chronic consumption of a high-calorie diet coupled with an altered sleep-wake cycle causes disruption of circadian clock that can impact the gut microbiome leading to metabolic syndrome and associated diseases. Herein, we investigate the effects of a high fat high fructose diet (H) alone or in combination with photoperiodic shifts induced chronodisruption (CD) on gut microbiota of C57BL/6J male mice. Further, the merits of daily evening intraperitoneal administration of melatonin in restoring gut microbiota are studied herein. Experimental groups viz. H, CD and HCD mice recorded higher levels of serum pro-inflammatory cytokines (TNF-α and IL-6) and lower levels of the anti-inflammatory cytokine, IL-10. These findings correlate with a concomitant increase in the transcripts of TLR4, TNF-α, and IL-6 in small intestine of the said groups. A decrement in mRNA levels of Ocln, ZO-1 and Vdr in these groups implied towards an altered gut permeability. These results were in agreement with the observed decrement in percentage abundance of total gut microflora and Firmicutes: Bacteroidetes (F/B) ratio. Melatonin administration accounted for lower-level inflammation (serum and gut) along with an improvement in gut permeability markers. The total abundance of gut microflora and F/B ratio showed an improvement in all the melatonin-treated groups and the same is the highlight of this study. Taken together, our study is the first to report perturbations in gut microbiota resulting due to a combination of photoperiodic shifts induced CD and a high fat high calorie diet-induced lifestyle disorder. Further, melatonin-mediated rejuvenation of gut microbiome provides prima facie evidence of its role in improving gut dysbiosis that needs a detailed scrutiny.

Circadian control of Nocturnin and its regulatory role in health and disease.

Circadian rhythms are generated by intrinsic 24-h oscillations that anticipate the extrinsic changes associated with solar day. A conserved transcriptional-translational feedback loop generates these molecular oscillations of clock genes at the organismal and the cellular levels. One of the recently discovered outputs of circadian clock is Nocturnin (Noct) or Ccrn4l. In mice, Noct mRNA is broadly expressed in cells throughout the body, with a particularly high-amplitude rhythm in liver. NOCT belongs to the EEP family of proteins with the closest similarity to the CCR4 family of deadenylases. Multiple studies have investigated the role of Nocturnin in development, adipogenesis, lipid metabolism, inflammation, osteogenesis, and obesity. Further, mice lacking Noct (Noct KO or Noct-/-) are protected from high-fat diet-induced obesity and hepatic steatosis. Recent studies had provided new insights by investigating various aspects of Nocturnin, ranging from its sub-cellular localization to identification of its target transcripts. However, a profound understanding of its molecular function remains elusive. This review article seeks to integrate the available literature into our current understanding of the functions of Nocturnin, their regulatory roles in key tissues and to throw light on the existing scientific lacunae.