From the health point of view, circadian rhythm is obviously a great deal of disruption is unfavorable, a lot of diseases may therefore find a chance to take advantage of, such as the incidence of hepatocellular carcinoma (HCC) in our country and the number of deaths is extremely high, before scholars believe that circadian rhythm is a major non-alcoholic fatty liver disease (NAFLD) related to the HCC of a large behind the scenes black hand.
Recently, Fu Loning's group at Baylor University School of Medicine published the latest research results in the well-known journal Journal of Hepatology, and found direct evidence that circadian rhythm disruption accelerates the development of NAFLD-associated HCC: experiments carried out on a mouse humanized liver model showed that circadian rhythm disruption can directly induce the development of NAFLD-associated HCC, and that the development of NAFLD-associated HCC can be accelerated by circadian rhythm disruption. NAFLD-associated HCC and accelerates distant metastasis of HCC through transcriptome reprogramming!
The study shows that regardless of the dietary status consumed by mice, circadian rhythm disruption can be an accomplice to NAFLD-associated HCC, and the molecular pathways and pathological features of mouse hepatocytes induced by circadian rhythm disruption are highly similar to those of human HCC patients, so gradually normalizing circadian rhythms can reduce the incidence and distant metastasis of HCC, so we have to start from the biological clock in the fight against liver cancer, too.
A chart summarizing the core of the paper
With the wave of obesity sweeping the world, NAFLD is approaching to become the most important causative factor of liver cancer, and some studies have predicted that by 2030, NAFLD, the "new generation of the devil", will take the place of hepatitis B/hepatitis C viruses , and the pathogenesis and disease characteristics of NAFLD-associated HCC are not very different from those of hepatitis virus-associated HCC. HCC.
Previously, many studies have shown that circadian rhythm disruption on lipid metabolism, glucose metabolism and intestinal flora, may contribute to NAFLD-associated HCC, but purely mouse experiments can be reflected in the extent of the impact on humans, or a huge unknown, after all, the biological clocks of humans and mice are very different.
So in the current study, researchers at Baylor University School of Medicine used the emerging humanized liver mouse model to more accurately assess the effects of circadian disruption. The experiments showed that mice subjected to an "8-hour night shift" (achieved by regulating light delivery) had a significantly shorter lifespan, significant signs of cirrhosis and jaundice, and significant development of HCC and distant metastases compared to mice subjected to a stable light/dark cycle.
Circadian rhythm disruption is sufficient to induce the development of HCC alone
Analysis of serum markers in mice showed that circadian rhythm disorder mice developed hyperglycemia and hyperinsulinemia before HCC was confirmed to be detected, and the levels of markers such as TNFα and IL-6, which are associated with liver injury, inflammation, and hepatic fibrosis, were significantly elevated, which was also consistent with the manifestations of human patients with cirrhosis or NAFLD.
Further dissection of mouse livers also observed pathologic changes similar to human NAFLD-associated HCC. In conclusion, experiments in mouse models of humanized liver were able to confirm that circadian rhythm disruption is sufficient to induce NAFLD-associated HCC alone.
RNA sequencing of cancerous hepatocytes showed that circadian disruption has a significant impact on gene expression in both parenchymal and non-parenchymal cells, focusing on a full spectrum of dysregulation at the level of the transcriptome: hepatocyte metabolism of glucose, bile acids, cholesterol, and other substances, as well as inflammatory responses, are not immune to circadian disruption, and even more so the epithelial-mesenchymal transition (EMT), metabolic reprogramming, More importantly, processes such as epithelial-mesenchymal transition (EMT), metabolic reprogramming, dysregulation of immune checkpoints and P53 signaling are directly linked to cellular carcinogenesis.
It can be said that circadian rhythm disruption in mice completely reproduces the typical pathogenic mechanisms of human NAFLD-associated HCC, and the transcriptomic manifestations of mouse hepatocytes and tumors are almost identical to the sequencing results of human patients, which confirms the value of the findings and supports the continuation of in-depth studies in humanized mouse models to elucidate the oncogenic mechanisms of circadian rhythm disruption, as well as other HCC promoters. and other oncogenic mechanisms of HCC.
Chronic circadian rhythm disruption activates various signature pathways in NAFLD-associated HCC
In addition, since circadian disorders lead to changes at various metabolic levels, measuring the levels of specific metabolites can be a relatively non-invasive way to track the progression of the cancer, and researchers have conducted specific analyses for this purpose, confirming that a variety of bile acids are consistently elevated during the progression of NAFLD to HCC, and can serve as prognostic markers for patients.
In conclusion, the role of circadian rhythm disorders in promoting the development of HCC has been clear, and because there is currently no specific treatment for NAFLD drugs have been successfully approved for marketing, want to rely on treatment to block NAFLD and then cut off the cancerous process is still relatively difficult, we are still from a good night's sleep, keep your mouth shut, and take a step forward, try to stay away from fatty liver and circadian rhythm disorders, don't let them hit the unsolvable streak. The only way to do this is to stay away from fatty liver and circadian rhythm disorders.
