Roles of the Circadian Rhythms in Metabolic Disease and Health

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (10 March 2023) | Viewed by 12157

Special Issue Editors


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Guest Editor
Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
Interests: diet; physical activity; sleep; circadian rhythms; metabolc syndrome; breast cancer

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Guest Editor
Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy
Interests: physical activity; sleep; circadian rhythms; rest-activity circadian rhythms; chronotypes; health

E-Mail Website
Guest Editor
Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy
Interests: physical activity; sleep; circadian rhythms; rest-activity circadian rhythms; chronotypes; health; eating disorders

Special Issue Information

Dear colleagues,

In recent years many studies have investigated the relationship between irregular circadian rhythms, abnormalities in the sleep-wake cycle, and metabolic risk factors, such as hypertension, obesity, dyslipidemia, diabetes and cancer. Circadian rhythms influence daily behavior and can change during the lifespan, both in physiological and pathological conditions; in fact, they can also be considered as markers of health or disease status. Modern jobs or/and lifestyles, such as shift work, exposure to prolonged hours of artificial light, reduction in physical activity levels, and bad nutrition, may negatively affect the human circadian system.

Chronobiology is the science that studies the temporal structure of organisms’ functions, analyzing the periodic oscillations of these biological phenomena. Since virtually all biological functions are subject to periodic variations, the potential areas of research are vast and include the medical as well as the strictly biological fields.

Therefore, this Special Issue of Metabolites will be dedicated to publishing current advances in the roles of the circadian rhythms in metabolic disease and health to address recent challenges, from basic periodic phenomena that characterise living organisms to the possibility of applying that knowledge to practical or clinical problems.

Dr. Eleonora Bruno
Dr. Lucia Castelli
Dr. Letizia Galasso
Guest Editors

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Published Papers (6 papers)

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13 pages, 2356 KiB  
Article
Circadian Disruption across Lifespan Impairs Glucose Homeostasis and Insulin Sensitivity in Adult Mice
by Tracy K. Her, Jin Li, Hao Lin, Dong Liu, Kate M. Root, Jean F. Regal, Emilyn U. Alejandro and Ruifeng Cao
Metabolites 2024, 14(2), 126; https://doi.org/10.3390/metabo14020126 - 16 Feb 2024
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Abstract
Circadian rhythm disruption is associated with impaired glucose homeostasis and type 2 diabetes. For example, night shift work is associated with an increased risk of gestational diabetes. However, the effects of chronic circadian disruption since early life on adult metabolic health trajectory remain [...] Read more.
Circadian rhythm disruption is associated with impaired glucose homeostasis and type 2 diabetes. For example, night shift work is associated with an increased risk of gestational diabetes. However, the effects of chronic circadian disruption since early life on adult metabolic health trajectory remain unknown. Here, using the “Short Day” (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was used to disrupt mouse circadian rhythms across the lifespan, we investigated glucose homeostasis in adult mice. Adult SD mice were fully entrained into the 8 h/8 h LD cycle, and control mice were entrained into the 12 h/12 h LD cycle. Under a normal chow diet, female and male SD mice displayed a normal body weight trajectory. However, female but not male SD mice under a normal chow diet displayed glucose intolerance and insulin resistance, which are associated with impaired insulin signaling/AKT in the skeletal muscle and liver. Under high-fat diet (HFD) challenges, male but not female SD mice demonstrated increased body weight gain compared to controls. Both male and female SD mice developed glucose intolerance under HFD. Taken together, these results demonstrate that environmental disruption of circadian rhythms contributes to obesity in a sexually dimorphic manner but increases the risk of glucose intolerance and insulin resistance in both males and females. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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20 pages, 2414 KiB  
Article
Changes in the Secretion of Melatonin and Selected Adipokines during the Progression of Parkinson’s Disease—Preliminary Studies
by Jan Milanowski, Kamil Kozerawski, Weronika Falęcka, Dominik Dudek, Beata Lisewska, Paweł Lisewski, Jarosław Nuszkiewicz, Roland Wesołowski, Jakub Wojtasik, Celestyna Mila-Kierzenkowska and Karolina Szewczyk-Golec
Metabolites 2023, 13(5), 668; https://doi.org/10.3390/metabo13050668 - 18 May 2023
Cited by 1 | Viewed by 1325
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases affecting elderly people. Considering the gap in the literature on melatonin and adipokine levels in PD patients at various stages of the disease, we conducted a study to investigate the levels of [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases affecting elderly people. Considering the gap in the literature on melatonin and adipokine levels in PD patients at various stages of the disease, we conducted a study to investigate the levels of selected parameters in PD patients at the disease’s early (ES) and advanced (AS) stages. Melatonin, leptin, adiponectin, and resistin concentrations were measured in the blood serum of 20 PD patients without dyskinesia (ES), 24 PD patients with dyskinesia (AS), and 20 healthy volunteers as a control group (CG). The data were analyzed using ANOVA. Melatonin was significantly lower in ES (p < 0.05) and higher in AS patients (p < 0.05) compared to CG. The level of leptin was increased both in ES (p < 0.001) and AS (p < 0.001) versus CG, while resistin was increased only in patients with dyskinesia (p < 0.05). Higher melatonin (p < 0.001) and resistin (p < 0.05) and lower leptin (p < 0.05) levels were found in AS versus ES. The main findings of the study include the changes in inflammatory markers’ levels during PD and a surprising increase in melatonin level in dyskinesia patients. Further research is necessary, which will be aimed at modulating the secretion of melatonin and adipokines as a treatment target for PD. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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14 pages, 821 KiB  
Article
Chronometabolism: The Timing of the Consumption of Meals Has a Greater Influence Than Glycemic Index (GI) on the Postprandial Metabolome
by Yi Ning Yong, Jiangwen Dong, Leroy Sivappiragasam Pakkiri, Christiani Jeyakumar Henry, Sumanto Haldar and Chester Lee Drum
Metabolites 2023, 13(4), 490; https://doi.org/10.3390/metabo13040490 - 29 Mar 2023
Cited by 1 | Viewed by 1631
Abstract
Eating late in the day is associated with circadian desynchrony, resulting in dysregulated metabolism and increased cardiometabolic disease risk. However, the underlying mechanisms remain unclear. Using targeted metabolomics of postprandial plasma samples from a secondary analysis of a randomised 2 × 2 crossover [...] Read more.
Eating late in the day is associated with circadian desynchrony, resulting in dysregulated metabolism and increased cardiometabolic disease risk. However, the underlying mechanisms remain unclear. Using targeted metabolomics of postprandial plasma samples from a secondary analysis of a randomised 2 × 2 crossover study in 36 healthy older Chinese adults, we have compared postprandial metabolic responses between high (HI) glycemic index (GI) or low-GI (LO) meals, consumed either at breakfast (BR) or at dinner (DI). 29 out of 234 plasma metabolites exhibited significant differences (p < 0.05) in postprandial AUC between BR and DI sessions, whereas only five metabolites were significantly different between HI and LO sessions. There were no significant interactions between intake timing and meal GI. Lower glutamine: glutamate ratio, lower lysine and higher trimethyllysine (TML) levels were found during DI compared with BR, along with greater postprandial reductions (δAUC) in creatine and ornithine levels during DI, indicating a worse metabolic state during the evening DI period. Greater reductions (δAUC) in postprandial creatine and ornithine were also observed during HI compared with LO (both p < 0.05). These metabolomic changes may indicate potential molecular signatures and/or pathways linking metabolic responses with cardiometabolic disease risk between different meal intake timings and/or meals with variable GI. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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10 pages, 950 KiB  
Article
Supplementation of L-Ornithine Could Increase Sleep-like Behavior in the Mouse Pups
by Mayumi Takakura, Satsuki Nagamachi, Takuma Nishigawa, Yoshihiro Takahashi and Mitsuhiro Furuse
Metabolites 2022, 12(12), 1241; https://doi.org/10.3390/metabo12121241 - 09 Dec 2022
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Abstract
Along the maternal–fetal–neonatal axis, one of the problems relating to the maternal–neonatal axis is infant sleep problems including nighttime crying. One possible solution could be to provide the newborn with sleep-promoting ingredients through breast milk or formula. So far, it has been reported [...] Read more.
Along the maternal–fetal–neonatal axis, one of the problems relating to the maternal–neonatal axis is infant sleep problems including nighttime crying. One possible solution could be to provide the newborn with sleep-promoting ingredients through breast milk or formula. So far, it has been reported that L-ornithine has a sleep-related effect. Therefore, we investigated the effect of dietary L-ornithine on maternal mouse plasma and milk L-ornithine levels in Experiment 1. In Experiment 2, a single dose of L-ornithine was applied to know the time-course changes in plasma, mammary gland and milk L-ornithine levels. Experiment 3 was conducted to confirm sleep behavior as well as changes in polyamine levels in milk. L-Ornithine levels in maternal plasma significantly increased by both dietary regimen and single oral administration in Experiments 1 and 2. Both L-ornithine treatments also increased its levels in milk, although not to a concentration as high as in plasma. In Experiment 3, the level of polyamines, which are metabolized from L-ornithine, did not significantly differ after L-ornithine administration. In sleep-like behavior observations, the average concentration of L-ornithine in milk did not increase the sleep-like behavior of mouse pups. However, more concentrated L-ornithine solutions can significantly increase sleep-like behavior. These results revealed that even if mothers ingested L-ornithine to increase L-ornithine levels in breast milk, it is difficult to promote sleep in newborns. Because it is difficult to raise L-ornithine in breast milk to sleep-inducing levels, L-ornithine added formula may partially improve infant sleep and has the potential for preventing infant sleep problems such as nighttime crying. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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14 pages, 1893 KiB  
Article
GlycA, a Biomarker of Low-Grade Inflammation, Is Increased in Male Night Shift Workers
by Daniele Bizzarri, Martijn E. T. Dollé, Bette Loef, Erik B. van den Akker and Linda W. M. van Kerkhof
Metabolites 2022, 12(12), 1172; https://doi.org/10.3390/metabo12121172 - 24 Nov 2022
Cited by 2 | Viewed by 2832
Abstract
Sustained night shift work is associated with various adverse health risks, including an increased risk of cardiovascular disease, type II diabetes, and susceptibility to infectious respiratory diseases. The extent of these adverse health effects, however, seems to greatly vary between night shift workers, [...] Read more.
Sustained night shift work is associated with various adverse health risks, including an increased risk of cardiovascular disease, type II diabetes, and susceptibility to infectious respiratory diseases. The extent of these adverse health effects, however, seems to greatly vary between night shift workers, yet the underlying reasons and the mechanisms underlying these interindividual differences remain poorly understood. Metabolomics assays in the blood have recently gained much attention as a minimally invasive biomarker platform capturing information predictive of metabolic and cardiovascular diseases. In this cross-sectional study, we explored and compared the metabolic profiles of 1010 night shift workers and 1010 age- and sex-matched day workers (non-shift workers) from the Lifelines Cohort Study. The metabolic profiles were determined using the 1H-NMR Nightingale platform for the quantification of 250 parameters of metabolism, including routine lipids, extensive lipoprotein subclasses, fatty acid composition, and various low-molecular metabolites, including amino acids, ketone bodies, and gluconeogenesis-related metabolites. Night shift workers had an increased BMI (26.6 vs. 25.9 kg/m2) compared with day workers (non-shift workers) in both sexes, were slightly more likely to be ever smokers (only in males) (54% vs. 46%), worked on average 5.9 ± 3.7 night shifts per month, and had been working in night shifts for 18.3 ± 10.5 years on average. We observed changes in several metabolic markers in male night shift workers compared with non-shift workers, but no changes were observed in women. In men, we observed higher levels of glycoprotein acetyls (GlycA), triglycerides, and fatty acids compared with non-shift workers. The changes were seen in the ratio of triglycerides and cholesterol(esters) to total lipids in different sizes of VLDL particles. Glycoprotein acetyls (GlycAs) are of particular interest as markers since they are known as biomarkers for low-grade chronic inflammation. When the analyses were adjusted for BMI, no significant associations were observed. Further studies are needed to better understand the relationship between night shift work and metabolic profiles, particularly with respect to the role of sex and BMI in this relationship. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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18 pages, 487 KiB  
Systematic Review
The Effect of Diet on the Cardiac Circadian Clock in Mice: A Systematic Review
by Ana Beatriz Rezende Paula, Letícia Teresinha Resende, Isabela Alcântara Barretto Araújo Jardim, Bianca Iara Campos Coelho, Denise de Coutinho Miranda, Alexandre Martins Oliveira Portes, Maria Cecília Teles, Ana Maria de Lauro Castrucci and Mauro César Isoldi
Metabolites 2022, 12(12), 1273; https://doi.org/10.3390/metabo12121273 - 15 Dec 2022
Cited by 1 | Viewed by 1969
Abstract
Circadian rhythms play important roles in regulating physiological and behavioral processes. These are adjusted by environmental cues, such as diet, which acts by synchronizing or attenuating the circadian rhythms of peripheral clocks, such as the liver, intestine, pancreas, white and brown adipose tissue, [...] Read more.
Circadian rhythms play important roles in regulating physiological and behavioral processes. These are adjusted by environmental cues, such as diet, which acts by synchronizing or attenuating the circadian rhythms of peripheral clocks, such as the liver, intestine, pancreas, white and brown adipose tissue, lungs, kidneys, as well as the heart. Some studies point to the influence of diet composition, feeding timing, and dietary restriction on metabolic homeostasis and circadian rhythms at various levels. Therefore, this systematic review aimed to discuss studies addressing the effect of diet on the heart clock in animal models and, additionally, the chronodisruption of the clock and its relation to the development of cardiovascular disorders in the last 15 years. A search was conducted in the PubMed, Scopus, and Embase databases. The PRISMA guide was used to construct the article. Nineteen studies met all inclusion and exclusion criteria. In summary, these studies have linked the circadian clock to cardiovascular health and suggested that maintaining a robust circadian system may reduce the risks of cardiometabolic and cardiovascular diseases. The effect of time-of-day-dependent eating on the modulation of circadian rhythms of the cardiac clock and energy homeostasis is notable, among its deleterious effects predominantly in the sleep (light) phase and/or at the end of the active phase. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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