Bmal1 Downregulation Exacerbates Age-Related Nonalcoholic Steatohepatitis By Promoting Nlrp3 Inflammasome Activation Via HIF-1Ɑ-Mediated Glycolysis
Nonalcoholic steatohepatitis (NASH) is a serious form of fatty liver disease that is not caused by alcohol, and it tends to be more severe in older individuals. Recent research sheds light on a crucial player in this process: a protein called BMAL1. Think of BMAL1 as a key component of your body’s internal clock, regulating daily rhythms that influence many bodily functions, including how your cells use energy.
This study found that when BMAL1 levels are lower, particularly in aging and when a high-fat diet is consumed, it significantly worsens NASH. The mechanism behind this involves a chain of events: lower BMAL1 leads to an overactive process where cells break down sugar for energy, known as glycolysis. This overactivity is influenced by another protein called HIF-1α, which helps cells adapt to changes in oxygen levels and also plays a role in metabolism. This heightened sugar metabolism then triggers a powerful inflammatory response in the liver, orchestrated by a protein complex called the NLRP3 inflammasome. It’s this inflammation that drives the progression and severity of NASH.
Essentially, the body’s internal clock, through BMAL1, plays a vital role in keeping liver inflammation in check. When this clock is disrupted, it can lead to a cascade of metabolic and inflammatory issues that exacerbate liver disease. These findings suggest that strategies aimed at restoring or boosting BMAL1 activity could offer a new approach to treating age-related NASH.
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