Living organisms present changes in their metabolism throughout the day, which are regulated by a mechanism known as the circadian clock [1]. The central circadian clock, the main regulator, is in the hypothalamic suprachiasmatic nucleus (SCN) and modulates body functions rhythmicity in synchrony with light and darkness as well as other daily signals such as food access, those signals are called Zeitgebers [2]. The circadian clock has a tight relationship with metabolic centers; in this way, people with desynchronization in their rhythms present abnormal eating behaviors and alterations in their metabolism [3]. This mechanism is also related to several diseases, including obesity, diabetes, anxiety, depression, and even cancer development [4].

Chrononutrition is an area of chronobiology that studies the relationship between food composition and the circadian clock [1]. Therefore, chronotherapies could be used to modulate related pathologies. In this way, chronobiotics—chemical substances that regulate the circadian clock, considered a therapy to re-entraining either short-term or long-term desynchronized circadian rhythms [5]- could be used to manage different diseases, with obesity as target. Obesity has become a global concern due to all the related comorbidities [6]. It is a multifactorial disease that involves factors such as lack of satiety and desynchronization of biological clocks. Alternative obesity therapies, such as satiety regulation by natural bioactive compounds, are gaining relevance [7]. Most bioactive compounds that modulate satiety signaling can exert chronobiotic effect, but there is a lack of evidence of how those two mechanisms are related.

Food intake is the result of many signaling integrations, such as hormones, nervous impulses, neurotransmitters, and their receptor interactions. Food and macronutrient ingestion are the first factors in determining satiety sensation throughout the day [8]. The presence or absence of macromolecules across the gastrointestinal tract (GIT) determines hormone secretion; there are several receptors for different molecules, for instance, glucose, free fatty acids, amino acids, and others [9]. Interaction of those molecules and their receptors activates hormone secretion; nevertheless, the production of each hormone will be different depending on the macronutrient crossing the GIT. Factors like timing, size of the meal, and environmental, psychological, social, and cultural aspects also influence satiety sensation [8]. Details of satiety hormone production, synthesis, and action mechanisms are presented in Table 1.

Hormone signaling must be integrated into the hypothalamus to exert an effect; vagal afferents are responsible for the signal between the GI tract and the hypothalamus [18]. Inside the arcuate nucleus hypothalamic region neurons signal orexigenic neurotransmitters such as neuropeptide Y (NPY) and Agouti-related peptide (AgRP). Still, there are also anorexigenic neurotransmitters like pro-opiomelanocortin (POMC). In this way, the GIT sends signals to the brain, which translates those signals and sends feedback to the GIT. This feedback loop generates the “Gut-Brain axis” [19]. According to macronutrient ingestion, satiety regulation will have different levels of success; several studies have proved the effect of each macronutrient over satiety signaling (Table 1).

Understanding the mechanism through which chronobiotics activate specific routes of the circadian clock and how those routes modulate satiety hormones or neurotransmissions can help discover effective therapies to treat or prevent pathologies such as obesity. This review compiles the evidence of natural chronobiotics, mainly polyphenols and short-chain fatty acids that affect the circadian clock mechanism and process modifications in genes or proteins resulting in signaling chain that modulates satiety hormones.