Discussion
obesity, depression, mitochondrial dysfunction, sleep disorders, NAFLD.Although hepatic steatosis, hypoxia, inflammation, snoring, insomnia, sleep-related, sleep traits, liver damage, nonalcoholic steatohepatitis, hepatic steatosis, Insomnia, NAFLD, OSA, liver inflammation, MR, steatosis
OBESITY, CARDIOVASCULAR DISEASE, INSULIN RESISTANCE, OXIDATIVE STRESS, BREAST CANCER, HYPOXIA, INFLAMMATION, ALTERNATION, MITOCHONDRIAL DYSFUNCTION, DISEASES, PATHOGENESIS, POSITIVE, LIVER FIBROSIS, LIVER DAMAGE, NONALCOHOLIC STEATOHEPATITIS, HEPATIC STEATOSIS, TUMOR NECROSIS, DISEASE, HYPOXIC, STEATOSIS
Many previous reports have used MR studies to determine the causal relationship between sleep-related problems and various diseases and indicators, such as cardiovascular disease, breast cancer, depression and glycated hemoglobin (In the MR analysis of this paper, we systematically evaluated the causal relationship between sleep traits and the onset of NAFLD, and demonstrated that different sleep traits can be the cause of the onset and exacerbation of NAFLD, and NAFLD does not change sleep traits, and the causal relationship between them is unidirectional. In addition to this, all previous observational clinical studies are difficult to avoid confounding risk factors due to the limitations of their own experimental methods, whereas in the present study, MR is less susceptible to measurement error, confounding, and reverse causality than traditional observational studies because the genotypes are robust and formed prior to the exposure factors (The pathogenesis of NAFLD is often described as a double whammy model. The first strike is characterized by increased intracellular triglyceride accumulation in hepatocytes due to adipose tissue lipolysis caused by obesity and insulin resistance. The second strike is characterized by the production of lipotoxic metabolites, oxidative stress, lipid peroxidation, mitochondrial dysfunction and the progression of liver inflammation and steatosis due to some genetic polymorphisms (In previous studies, most researchers have targeted the relationship between obstructive sleep apnea(OSA), which is characterized by snoring, and NAFLD. It has been extensively demonstrated experimentally that chronic intermittent hypoxia in OSA may be related to the pathogenesis and severity of NAFLD. In the hypoxic environment of OSA, adipose tissue lipolysis, oxidative stress, inflammation and liver fibrosis are increased (Therefore, it seems biologically plausible that OSA may exacerbate liver damage in NAFLD, leading to a phenotypic shift toward nonalcoholic steatohepatitis and liver fibrosis. However, the damage caused by OSA in NAFLD is due to hypoxia rather than the effects of sleep itself, which does not fully explain the mechanism of the damage caused by poor sleep habits in the body. Moreover, improving hypoxia alone does not provide a comprehensive treatment for NAFLD.Although hepatic steatosis is a reversible disease, Continuous Positive Airway Pressure(CPAP) does not seem to improve the morphological changes of the liver in patients with OSA (Therefore, we should focus on the impact that sleep itself has on NAFLD.In order to clearly understand the mechanisms of sleep, it is necessary to recognize that sleep is part of a 24-hour cycle that is largely regulated by the inevitable cycles of light and darkness. The light and dark cycles due to the rotation of the Earth are the main effect on living things. The periodic alternation of light and dark is the basis of the biological clock, which is ubiquitous in human physiology and behavior. The alignment of sleep and wakefulness with circadian cycles is essential for establishing a healthy sleep cycle. Dysregulation of these environmental changes (e.g., in night shift work) often leads to sleep disorders and pre-sleep symptoms such as insomnia. Fluctuations in cognitive ability and energy over a 24-hour period, as well as the urge to sleep after 14-16 hours of wakefulness, are familiar daily experiences. However, how the biological clock is intertwined with almost every aspect of physiological function, from cells to organs, is not as evident. Well-known physiological cycles include the sleep-wake cycle, the 24-hour temperature cycle, and the secretion of cortisol.The biological clock plays an important role in metabolic rhythms, such as glucose and lipid homeostasis (The relevant SNPs obtained from our study also proved our conjecture to some extent. The SNPs we obtained corresponded to a variety of genes, including FTO, RFX3 and KSR2, which are closely related to metabolism and insulin secretion.For example, FTO expression is increased in NAFLD, and it promotes hepatic steatosis by targeting PPARα (Insomnia means less sleep, which causes the body to produce more interleukin 6 and tumor necrosis factor, and also activates STAT family proteins (