Sleep Linked to Protection Against Nonalcoholic Fatty Liver Disease

Lack of sleep appears to be associated with the risk of nonalcoholic fatty liver disease (NAFLD), according to a new study, but “catch-up” sleep amy lower the risk.

The findings could help scientists better understand NAFLD and the implications of sleep on the disease. The report was published in the Annals of Hepatology.

NAFLD is a broad term for a wide variety of conditions caused by the excessive accumulation of fat. It comes with an increased risk of other metabolic conditions, such as diabetes and obesity.

Sleep — and sleep duration, in particular — is increasingly being identified as playing a role in a number of chronic conditions, wrote corresponding author Sangheun Lee, Ph.D., of the Catholic Kwandong University College of Medicine in South Korea. Recent evidence suggests the risk of NAFLD may be itself affected by sleep.

“Insufficient sleep, as well as poor sleep quality, can trigger several pathophysiological processes that are associated with NAFLD,” the authors noted.

Yet Lee and colleagues said while a broad association between NAFLD and sleep duration has been studied, there is less of an understanding of how certain sleep patterns affect (or potentially cause) NAFLD. One sleep pattern — weekend catch-up sleep (WCUS) — is an increasingly common behavior, the authors said. The term refers to the pattern of getting insufficient sleep during the workweek, but then sleeping for extra long periods of time on weekends in order to catch up.

The investigators decided to examine data from the Korea National Health and Nutrition Examination Survey, a survey that involved more than 100,000 patients in South Korea who enrolled between 2008 and 2019.

Survey respondents were grouped into three categories: patients who slept for less than seven hours per night on average; patients who slept for less than seven hours per night on weeknights, but more than seven hours per night on weekends; and patients who slept more than seven hours per week, on average.

The investigators found a significant negative relationship between sleeping more than seven hours per night and risk of NAFLD. Using a hepatic steatosis index (HSI) score of 36 or higher as an indicator of a fatty liver, the investigators found patients who got less than seven hours of sleep were significantly more likely to have fatty livers. When the authors used a more recent subset of the data (one that included weekend sleep behavior), they found the same association. The finding was true for both male and female subjects.

Lee and colleagues said there are several possible reasons for the relationship between NAFLD and sleep. They noted that the hypothalamic-pituitary-adrenal axis and the autonomic nervous system are key to the regulation of physical and mental health.

“Cortisol, inflammatory cytokines, and norepinephrine, which are derivatives of these systems, are associated with the variation in sleep such as total sleep time, sleep quality, sleep efficiency, and circadian midpoint,” the authors wrote. “The dysregulation of this axis caused by changes in sleep can increase the risk of NAFLD onset.”

They added that sleep duration is tied to leptin concentration, and leptin is associated with metabolic disease.

“A decrease in sleep duration results in a decrease in leptin concentration and an increase in the activity of the food reward system,” they said. “This leads to an increase in calorie intake and weight gain.”

Lee and colleagues noted that seven hours or more of sleep on weekdays and weekends and having WCUS were negatively correlated with obesity in the study.

However, the investigators said it is not clear whether “catch-up” sleep can ameliorate the increased risk of NAFLD.

“No research has shown how WCUS relieves the fatty liver in animal experiments and other clinical studies, however, we have suggested that sleep supplementation during weekends may ease oxidative stress and inflammation in the liver,” they wrote.

Lee and colleagues concluded that additional research should be done to find out the causal relationship, if any, between NAFLD and sleep. They said such research could lead to an expansion of therapeutic options for NAFLD, which are currently limited to weight loss and improving eating habits.