Circadian rhythms are innate processes within every living organism. These rhythms are internal clocks that act constantly in approximately 24-hour cycles that regulate and coordinate numerous bodily processes in response to the external environment. The mammalian literature has, by and large, focused on the core clock neurons located deep within the brain in the suprachiasmatic nucleus of the hypothalamus and many circadian inputs that allow for proper alignment of behaviors and processes with external stimuli in the surrounding environment. However, there has been considerably minimal research looking at circadian outputs. One such process in humans and other mammals that receives information from circadian rhythms is feeding behaviors. The two articles that will be discussed below are focused on this relationship between circadian rhythms and feeding behaviors. The first research group is primarily focused on ascertaining circadian outputs that regulate feeding: fasting rhythms, while the second research group assesses recent research aimed at understanding the relations between circadian rhythms, feeding behaviors, and gastrointestinal microbiota.
In the article, “A circadian output center controlling feeding: fasting rhythms in Drosophila”, by Daniel Cavanaugh and colleagues, the researchers addressed the need to improve understanding in the literature of circadian outputs with specific neuronal regulators in feeding behavior. Their principal focus was to assess a couple of neuronal populations downstream of core clock neurons in a putative output hub of circadian signaling in the Drosophila melanogaster pars intercerebralis (PI). Here, Cavanaugh and colleagues utilized a newly developed food monitor system FLIC to make immediate observations of feeding behavior and any potential changes as a result of genetic manipulations to the genes encoding for DILP+ and SIFa+ PI neurons. Their results suggested that altered levels of the neuropeptide SIFamide and mutated SIFa genes lead to a breakdown of normal feeding: fasting rhythms observed in Drosophila. In contrast, altering the neurons producing DILPs appeared to enhance total food intake but left the feeding rhythms untouched and unaffected. Cavanaugh and colleagues assert that this illustrates a double dissociation between these controlling neuronal populations for homeostatic and circadian regulation of feeding behaviors. Ultimately, while having determined some of the circadian outputs regulating feeding behavior, it appears likely that there are more distinct neuronal populations at work as feeding behaviors are not completely altered by just SIFa gene mutations and DILP manipulations alone.
In the article, “Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health”, by Jennifer Kaczmarek and colleagues, the researchers conducted a review of the interplay between the microorganisms in the gastrointestinal tract (GI), feeding and eating, and circadian rhythms of mice and humans. The authors made a point of discussing the relative novelty of this area of research as well as its relevance for maintaining good health and wellbeing. The time and quantity of food consumed have been found to be key factors that influence the GI microbiome. Further, Kaczmarek and colleagues described the recent findings of these gut microbiota as having circadian rhythms of their own. Circadian rhythms are of particular importance for health as their misalignment alters feeding: fasting rhythms and may lead to negative outcomes such as the substantially greater risk for becoming obese and developing metabolic syndrome. The richness and evenness of the GI microbial composition are greatly disrupted by erroneously feeding during fasting time and major diet changes. The most robust evidence of this mentioned by Kaczmarek and colleagues comes from mice studies. In mice, researchers have found that specific ratios of microbial species become abnormal and fluctuate improperly with misaligned rhythms and subsequently hinder realignment due to the compositional changes within the microbiota. In terms of metabolism, the impacts can include hormonal changes and increased storage of nutrients to even obese qualifications. Taken together, the GI microbiota in our GI tract possibly moderates circadian rhythms and overall health in humans as well. The few human studies that have been performed hint at results that mimic those in mice studies but lack substantiality due to smaller sample sizes and the greater costs and difficulties of conducting human research.
Both articles examine how feeding behaviors are regulated to a significant extent by circadian rhythms. Cavanaugh and colleagues performed genetic manipulations impacting circadian rhythms and feeding behaviors and determined two neuronal populations acting as circadian outputs, SIFamide and DILP, with distinctive regulatory roles. While Kaczmarek and colleagues presented a large-scale review that indicates how our GI microbiota is likely to influence circadian rhythms and be influenced by those same rhythms. Despite not directly studying circadian rhythms in humans, Drosophila melanogaster and mice share analogous structures and genes that are believed to have strong potential to translate into clinical research with humans.
Citations:
Dreyer, A. P., Martin, M. M., Fulgham, C. V., Jabr, D. A., Bai, L., Beshel, J., Cavanaugh, D. J. (2019). A circadian output center controlling feeding:fasting rhythms in Drosophila. PLOS Genetics, 15(11). https://doi.org/10.1371/journal.pgen.1008478
Kaczmarek, J. L., Thompson, S. V., Holscher, H. D. (2017). Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health. Nutrition Reviews, 75(9), 673–682. https://doi.org/10.1093/nutrit/nux036
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