Circadian rhythms can be defined as a cycle that occurs roughly within 24 hours that largely affect behavioral and physiological activities within organisms. The patterns produced by circadian rhythms are predictable and correspond to external stimuli, temperature and exercise, but primarily light. Circadian rhythms affect body temperature, sleep, hormone release, and cognitive function. One of the most important processes that is affected and studied is feeding patterns. Dr. Daniel Cavanaugh's recent article "Central and Peripheral Clock Control of Circadian Rhythms" especially focuses on the feeding patterns of organisms, specifically Drosophila melanogaster and its relations to peripheral and central clocks. Another article that targets feeding patterns, "Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption", written by Dr. Girish Malkani, attempts to use time restricted feeding in order to counteract obesity within Drosophila melanogaster. Both these articles have many parallels, although both attempt to achieve different goals.
In a Drosophila's circadian clock, the neurons contain 4 components. 2 of the 4 are transcription factors clock (CLK) and cycle (CYC) components. These factors bind to DNA to regulate genes. CLK and CYC activate timeless (TIM) and period (PER). After proteins are created, they inhibit their own transcription. This process regulates the oscillation of circadian rhythms in all organisms. These molecular clocks are present throughout the body, not just the brain, known as peripheral circadian rhythms rather than the centeral circadian rhythms found in the brain. Cavanaugh tested feeding patterns by using GAL4-UAS system in order to target the fat body gene, which will be used to observe peripheral clocks and the brain clock gene to observe the central clocks. These genes are manipulated in order to regulate the speed at which the clock oscillates. When slowing down and speeding up the central brain clock, Cavanaugh and his researchers observed an offset in both variables, in which the GAL4 that slows down the rhythm displays a later period and the GAL4 that speeds up the rhythm displays an earlier period. Therefore, the central brain clock plays a role in feeding patterns. When the same manipulation is done on the peripheral brain clocks, the periods of feeding patterns do not change. Therefore, peripheral body clocks are not relevant to the feeding cycle. The next part of the experiment uses CRISPR to cut out PER and TIM from the central and peripheral body clocks. When PER and TIM were removed from the central body clock, the feeding patterns were extremely irregular and abnormal. However, when the same process was done on the peripheral body clock, the feeding patterns stayed intact. This implies that the central body clock in Drosophila plays a role in feeding patterns while the peripheral body clock does not.
Malkani's article argues that circadian rhythm disruption (CRD) is surfacing as a novel risk factor for obesity. The article states how feedback loops relating to circadian rhythms rely on external stimuli like feeding patterns, light-dark sensors, and sleep disruption. Malkani states, "Accordingly, constant light, aberrant eating schedules, and sleep disruption all predispose individuals to obesity-associated dysfunction and exacerbate the resulting phenotypes." When experimenters placed Drosophila under TRF conditions, flight performance increased, indicating a lack of weight gain. However, when put under the same TRF conditions as well as constant light (LL) conditions, the flies had a reduction in flight performance. A decline in locomotion is an indicator of obesity, therefore proving that CRD could result in obesity. The article hypothesizes that TRF mimics the feeding pattern that a circadian rhythm offers organisms, therefore anabolic or catabolic pathways involved in feeding would only need to be activated during the feeding or restricting periods of time.
Using both these articles, one can make an inference that the body clock used in Malkani's article must have been in the central body clock, as Cavanaugh's article discusses the sole role of central body clocks in feeding patterns, and the lack of involvement of the peripheral body clock. An interesting future endeavor that would use both articles would be whether peripheral body clocks are relevant in CRD-induced obesity by using techniques like GAL4 and CRISPR in order to isolate components of the peripheral body clock.
References
Fulgham, C. V., Dreyer, A. P., Nasseri, A., Miller, A. N., Love, J., Martin, M. M., Jabr, D. A., Saurabh, S., & Cavanaugh, D. J. (2021). Central and Peripheral Clock Control of Circadian Feeding Rhythms. Journal of biological rhythms, 36(6), 548–566. https://doi.org/10.1177/07487304211045835
Villanueva, J.E., Livelo, C., Trujillo, A.S. et al. Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption. Nat Commun10, 2700 (2019). https://doi.org/10.1038/s41467-019-10563-9
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