The role of circadian clocks in the pathogenesis of NAFLD

The circadian clock controls rhythms responsible for regulating bodily functions, e.g., appropriate eating times. When this clock becomes disrupted due to factors such as irregular daily eating patterns or weekly schedules, it instead promotes lipid dysregulation, oxidative stress, and inflammation.

Comment:

The circadian clock controls rhythms responsible for regulating bodily functions, e.g., appropriate eating times. When this clock becomes disrupted due to factors such as irregular daily eating patterns or weekly schedules, it instead promotes lipid dysregulation, oxidative stress, and inflammation. Animal models have demonstrated that metabolic health is determined by what and, importantly, when we eat. A dysregulated circadian clock influenced by disrupted diet timings have been shown to influence hepatic fat accumulation. 

All these features, from lipid dysregulation to steatosis, are characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), its progressive form.

Despite this, current management of NAFLD focuses solely on dietary intake and physical activity without considering behavioural and dietary approaches to regulating patients’ circadian biological rhythms.

The aim of this review is to highlight the impact of circadian rhythms and sleep patterns on the pathogenesis of NAFLD. It also assesses dietary approaches to realign lifestyle habits with the circadian clock (e.g., chrononutrition) and its value in the management of NAFLD.

Key learnings:

The central circadian clock resides in the suprachiasmatic nuclei (SCN), which synchronises with the liver peripheral clock to regulate hepatic metabolism. Disruptions in this synchronisation or the absence of a functional hepatic circadian clock increases susceptibility to metabolic abnormalities, including insulin resistance and increased adiposity. Both metabolic disturbances possess a direct association with NAFLD and fibrosis, which leads to NASH.

Along with regulating important hepatic processes, the SCN also creates activity (day-time) and resting (night-time) phases, which may be disrupted by artificial lights. Studies into workers continuously exposed to night shifts underscore an association between shift work and higher NAFLD prevalence. 

Studies into the association between sleep disturbance and NAFLD progression yield inconclusive results. It is known that patients with NAFLD and cirrhotic patients possess poor sleep quality with delayed sleep onset. While some studies conclude that short sleep durations are protective against NAFLD onset, several recent articles suggest that individuals with sleep durations of less than 6 hours possess a small, significant increase in the risk of developing NAFLD.

Approaches to amend circadian clocks include chrononutrition, which advocates for regular eating behaviours and the absence of late-night eating. Strategies combining chrononutrition with healthy sleep patterns according to biological clocks may thus be pivotal to combatting NAFLD. Future research should develop effective feeding and sleeping strategies for the management of NAFLD patients.

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Dr. S Duarte

Dr. S Duarte

Articles: 56

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