Circadian Rhythms, Obesity, and Weight Loss (CLOCK)

CLOCK gene is a core component of the biological clock. It is one of the main genes responsible for human daily rhythms, also known as circadian rhythms [R].

Many processes in the body follow a daily rhythm, which is why CLOCK has many and varied effects. To name a few, mutations in this gene have been linked to:

• Being an evening person [R, R, R]
• Sleep patterns and insomnia [R, R]
• Obesity and weight loss [R, R, R, R]
• ADHD [R, R]
• Schizophrenia [R]
• Insulin levels, metabolic syndrome, and diabetes [R, R, R]
• Alzheimer’s [R]

In this article, we will focus on CLOCK‘s role in obesity and weight loss. 

CLOCK gene is one of the main components of the biological clock. This means it’s responsible for our daily rhythms. Mutations in this gene have been linked to sleep patterns, metabolic disorders, and body weight. 

The rs1801260 is the most studied SNP in the CLOCK gene. Several studies have found that people carrying the ‘G’ variant of rs1801260 [R, R, R, R, R]:

• are more likely to be obese
• have greater difficulties in controlling and losing weight
• do worse in dietary weight loss interventions

This is especially of interest because there’s an estimate that about 46% of the U.S. population have this SNP [R]!

In a study with 284 people, this SNP was not linked to obesity directly. However, overweight and obese people with the ‘GG’ genotype had significantly higer BMI, compared to those with ‘AG’ and or ‘AA’ genotypes. Moreover, extremely obese people were more likely to have the ‘GG’ genotype and the ‘G’ allele compared to less obese individuals [R]. 

However, there are also some contradictory studies. Scientists found no link between this SNP and body weight in a study with children, while a link to lower body weight was found in elderly and in people with eating disorders [R, R, R, R]. 

There is definitely more that we need to learn about the role of this gene in obesity, and why it seems to affect different life stages in different ways.

A SNP in the CLOCK gene has been associated with obesity, higher BMI, difficulty losing weight, and doing worse in dietary interventions.

There is a link between how the CLOCK gene affects circadian rhythms and sleep on one hand, and metabolic balance and eating behavior on the other [R, R].

Studies have found that sleep deprivation disrupts metabolism by increasing the levels of the stress hormone cortisol and decreasing insulin sensitivity. Furthermore, a lack of sleep increases the levels of the hunger hormone ghrelin, which increases hunger and appetite — thereby increasing the risk of obesity [R, R, R, R, R, R].

The rs1801260 ‘G’ allele has been associated with:

• Abnormal and less stable circadian rhythms [R, R]
• Shorter sleep duration (≤6 h per day) [R, R, R]
• Being an evening person [R, R, R]
• Less activity overall, being active later in the day, and being sleepier during the day [R, R]
• Having breakfast late [R]
• Higher ghrelin (hunger hormone) levels and lower satiety [R, R]
• Higher insulin and insulin resistance [R]
• Low compliance with dietary programs, such as the Mediterranean diet [R]

According to another theory, CLOCK variants may affect body weight and metabolic processes through the parasympathetic nervous system. Low sympathetic activity and high parasympathetic activity decrease energy expenditure, which increases the risk of obesity [R, R]. 

But the truth is that the scientists still haven’t figured out how exactly CLOCK relates to weight. For example, the ‘G’ allele of rs1801260 increases CLOCK activity over 24h. However, studies are in disagreement as to whether a higher or a lower CLOCK activity predisposes to obesity [R, R, R]. 

Future studies will need to look at when (e.g. morning, evening) this gene is active and in which tissues (e.g. brain, fat tissue) to provide better answers. We’ll keep you posted on new discoveries!

CLOCK may have an effect on body weight by affecting sleep patterns or by increasing parasympathetic activity. The rs1801260 ‘G’ variant has been linked to abnormal circadian rhythms, shorter sleep duration, elevated levels of the hunger hormone ghrelin, and higher insulin resistance — all of which can be linked to obesity. 

CLOCK rs1801260:

• ‘GG’ = Associated with obesity, higher BMI in those who are obese, and difficulty losing weight.
• ‘AG’ = Associated with obesity, higher BMI in those who are obese, and difficulty losing weight.
• ‘AA’ = Not associated with obesity.

Around 39% of people around the world carry the ‘G’ allele, while 7% have the ‘GG’ genotype. The ‘G’ allele is more common in Europe and in South Asia, where over 50% of people are carriers. 

It’s estimated that about 46% of the U.S. population has the ‘G’ variant [R].