1.
Circadian cycle
It is believed that the Earth's rotation cycle allowed organisms to adapt to
predictable variations in light and temperature in the environment they inhabit.
Because of these variations, which occur in a cycle of approximately 24 hours, there
was the evolution of so-called circadian cycles (from the Latin, "circa" = about,
"diem" = day), and are capable of regulating several biochemical and behavioral
processes in the duration of the day and night cycle (Bollinger and Schibler, 2014;
Franzago et al., 2023).
Circadian control mechanisms are found in almost all regions of the brain and
peripheral organs that participate in nutrient metabolism, proving to be essential for
maintaining metabolic homeostasis (Chaix et al., 2019; Pickel and Sung, 2020). In
mammals, the circadian system works in a hierarchical manner. The suprachiasmatic
nucleus (SCN), located in the hypothalamus, is the main regulator of the circadian
cycle. Its timing is done through light information, which is captured by
photoreceptors in the retina and transmitted to the SCN. In the absence of
brightness, the pineal gland is stimulated to synthesize and secrete melatonin, which
signals light/dark information to peripheral tissues (Lack and Wright, 2007; Potter et
al., 2016). In this way, it is possible to regulate behavioral rhythms such as the
sleep-wake cycle and moments of fasting/eating, as well as physiological rhythms
such as the regulation of body temperature, endocrine functions and catabolism and
anabolism cycles (Franzago et al., 2023 ) .
This timing is also observed at the molecular level, and is based on two
feedback loops in gene expression that are interconnected (Bollinger and Schibler,
2014). They are mediated by the transcription factors BMAL1 and CLOCK, which
heterodimerize and form the CLOCK/BMAL1 complex. This complex binds to the
E-box binding sites, activating the expression of the Period (PER) and Cryptochrome
(CRY) gene families. PER and CRY proteins creates complexes with polypeptides
and once these complexes reach a critical concentration, they bind to
CLOCK/BMAL1, inhibiting its activity. Over time, PER/CRY levels become too low to
maintain negative feedback and CLOCK and BMAL1 begin to complex again,
restarting the cycle. At the same time, a second feedback loop takes place, with
CLOCK/BMAL1 regulating its own transcription. This happens by activating the
transcription of the nuclear receptor-specific genes REV-ERB and ROR, which serve
as regulators of BMAL1 transcription (Asher and Sassone-Corsi, 2015; Bollinger and
Schibler, 2014; Chaix et al., 2019).
Although it can be said to be the main pacemaker, the SCN rarely has
complete control over the circadian rhythm. Even though it is a system capable of
maintaining autonomy, the circadian rhythm is notable for its plasticity and can be
modulated by external signals called zeitgebers (Kuhlman et al., 2018; Potter et al.,
2016). Ambient light is considered the most powerful zeitgeber, directly influencing
the SCN through its variations in timing, duration, intensity and wavelength. For
rhythms in peripheral tissues, other zeitgebers are more influential, such as ambient
temperature, physical activity, hormonal levels and mainly factors related to food,
such as time, frequency and composition of meals (Mohd Azmi et al., 2020;
Grosjean et al ., 2023).
The circadian cycle is a system that evolved with the purpose of optimizing
the metabolism of energy and nutrients depending on external factors. For
physiological processes to occur properly, this system must be aligned according to
the environment: the system is expected to stimulate sleep and anabolic functions
during the night, and wakefulness and catabolic functions during the day (Mohd Azmi
et al., 2020). However, the central and peripheral cycles are stimulated by different
zeitgebers and consequently become misaligned. Circadian misalignment causes
detrimental impacts on metabolic, physiological, and behavioral processes (Fatima
and Rana, 2020).
2. Circadian disorders and the emergence of chronic non-communicable
diseases
Disturbances in the circadian rhythm arise as a consequence of chronic
exposure to factors that misalign the circadian cycle. There are several factors that
contribute to the emergence of these disorders, such as endogenous factors
(advanced or delayed sleep phase syndrome and other disorders) and exogenous
factors (exposure to bright light at night, meals at inappropriate times, short periods
of sleep, poor sleep quality) (Poggiogalle et al., 2017; Zhu and Lee, 2012). These
disorders directly impact the homeostasis of certain metabolic pathways, becoming
risk factors for the emergence of chronic non-communicable diseases (NCDs) or
their worsening (Sarkisian et al., 2017).
It is understood that NCDs are non-contagious, multifactorial diseases that
can last for long periods of time, and are generally difficult to cure (Piovani et al.,
2022). They represent a major public health problem, being the main causes of
morbidity, mortality and early mortality (before the age of 70) (VIGITEL, 2019). In
2019, it was estimated that 73.6% of global deaths were due to some NCD; In Brazil,
this data is equally relevant, with 41.8% of deaths. Among NCDs, cardiovascular
diseases, diabetes, neoplasms and respiratory diseases stand out (VIGITEL, 2020).
According to the World Health Organization (WHO), the worsening of NCDs is due to
a set of risk factors: smoking, physical inactivity, excessive alcohol use and
inadequate food consumption. Among these, the risks arising from an unhealthy diet
are considered to have the greatest impact (OPAS, 2016).
Generally, an unhealthy diet is considered one that is rich in sodium, sugar,
saturated and trans fats, processed and ultra-processed foods, and low in fruits and
vegetables (OPAS, 2016). However, recent findings on metabolic changes resulting
from circadian disorders lead us to believe that meal times are as important as the
nutritional constitution of food (Asher and Sassone-Corsi, 2015; Franzago et al.,
2023).
