Search Results (7)

The chronotype, the personal predisposition towards morning or evening activities, significantly influences health conditions, sleep, and eating regulations. Individuals with evening chronotypes are often at a higher risk for weight gain due to misalignment between their natural tendencies of functioning and social schedules, resulting in insufficient sleep, disruptions in eating habits, and decreased physical activity levels. Often, impaired glucose tolerance and changes in melatonin, adiponectin, and leptin secretion, along with alterations in the clock gene functions in subjects with evening preferences, may be predisposed to obesity. These disturbances contribute to metabolic dysregulation, which may lead to the subsequent onset of obesity complications, such as hypertension, type 2 diabetes, sleep apnea, and liver diseases. Targeting critical components of the circadian system and synchronizing people’s chronotypes with lifestyle conditions could deliver potential strategies for preventing and treating metabolic disorders. Thus, it is recommended to take a personalized chronobiological approach to maintain a normal body weight and metabolic health. Nevertheless, future studies are needed to identify the clear mechanisms between the chronotype and human health. This article provides a narrative review and discussion of recent data to summarize studies on the circadian rhythm in the context of obesity. The manuscript represents a comprehensive overview conducted between August and November 2024 using the National Library of Medicine browser (Medline, Pub-Med, Web of Science). Full article

Type 2 diabetes is one of the leading threats to human health in the 21st century. It is a metabolic disorder characterized by a dysregulated glucose metabolism resulting from impaired insulin secretion or insulin resistance. More recently, accumulated epidemiological and animal model studies have confirmed that circadian dysfunction caused by shift work, late meal timing, and sleep loss leads to type 2 diabetes. Circadian rhythms, 24-h endogenous biological oscillations, are a fundamental feature of nearly all organisms and control many physiological and cellular functions. In mammals, light synchronizes brain clocks and feeding is a main stimulus that synchronizes the peripheral clocks in metabolic tissues, such as liver, pancreas, muscles, and adipose tissues. Circadian arrhythmia causes the loss of synchrony of the clocks of these metabolic tissues and leads to an impaired pancreas β-cell metabolism coupled with altered insulin secretion. In addition to these, gut microbes and circadian rhythms are intertwined via metabolic regulation. Omics approaches play a significant role in unraveling how a disrupted circadian metabolism causes type 2 diabetes. In the present review, we emphasize the discoveries of several genes, proteins, and metabolites that contribute to the emergence of type 2 diabetes mellitus (T2D). The implications of these discoveries for comprehending the circadian clock network in T2D may lead to new therapeutic solutions. Full article

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice. Full article

Seasonality is gaining attention in the modulation of some physiological and metabolic functions in mammals. Furthermore, the consumption of natural compounds, such as GSPE, is steadily increasing. Consequently, in order to study the interaction of seasonal variations in day length over natural compounds’ molecular effects, we carried out an animal study using photo-sensitive rats which were chronically exposed for 9 weeks to three photoperiods (L6, L18, and L12) in order to mimic the day length of different seasons (winter/summer/and autumn-spring). In parallel, animals were also treated either with GSPE 25 (mg/kg) or vehicle (VH) for 4 weeks. Interestingly, a seasonal-dependent GSPE modulation on the hepatic glucose and lipid metabolism was observed. For example, some metabolic genes from the liver (SREBP-1c, Gk, Acacα) changed their expression due to seasonality. Furthermore, the metabolomic results also indicated a seasonal influence on the GSPE effects associated with glucose-6-phosphate, D-glucose, and D-ribose, among others. These differential effects, which were also reflected in some plasmatic parameters (i.e., glucose and triglycerides) and hormones (corticosterone and melatonin), were also associated with significant changes in the expression of several hepatic circadian clock genes (Bmal1, Cry1, and Nr1d1) and ER stress genes (Atf6, Grp78, and Chop). Our results point out the importance of circannual rhythms in regulating metabolic homeostasis and suggest that seasonal variations (long or short photoperiods) affect hepatic metabolism in rats. Furthermore, they suggest that procyanidin consumption could be useful for the modulation of the photoperiod-dependent changes on glucose and lipid metabolism, whose alterations could be related to metabolic diseases (e.g., diabetes, obesity, and cardiovascular disease). Furthermore, even though the GSPE effect is not restricted to a specific photoperiod, our results suggest a more significant effect in the L18 condition. Full article

Lengthening the daily eating period contributes to the onset of obesity and metabolic syndrome. Dietary approaches, including energy restriction and time-restricted feeding, are promising methods to combat metabolic disorders. This study explored the effect of early and late time-restricted feeding (TRF) on weight and adiposity, food consumption, glycemic control, clock gene expression, and liver metabolite composition in diurnal Nile grass rats (NGRs). Adult male and female Nile grass rats were randomly assigned to one of three groups: (1) access to a 60% high-fat (HF) diet ad-libitum (HF-AD), (2) time-restricted access to the HF diet for the first 6 h of the 12 h light/active phase (HF-AM) or (3) the second 6 h of the 12 h light/active phase (HF-PM). Animals remained on their respective protocols for six weeks. TRF reduced total energy consumption and weight gain, and early TRF (HF-AM) reduced fasting blood glucose, restored Per1 expression, and reduced liver lipid levels. Although sex-dependent differences were observed for fat storage and lipid composition, TRF improved metabolic parameters in both male and female NGRs. In conclusion, this study demonstrated that early TRF protocol benefits weight management, improves lipid and glycemic control, and restores clock gene expression in NGRs. Full article

Circadian clocks control several homeostatic processes in mammals through internal molecular mechanisms. Chronic perturbation of circadian rhythms is associated with metabolic diseases and increased cancer risk, including liver cancer. The hepatic physiology follows a daily rhythm, driven by clock genes that control the expression of several proteins involved in distinct metabolic pathways. Alteration of the liver clock results in metabolic disorders, such as non-alcoholic fatty liver diseases (NAFLD) and impaired glucose metabolism, that can trigger the activation of oncogenic pathways, inducing spontaneous hepatocarcinoma (HCC). In this review, we provide an overview of the role of the liver clock in the metabolic and oncogenic changes that lead to HCC and discuss new potentially useful targets for prevention and management of HCC. Full article

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6 meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock, but did have mild effects on peripheral clocks. In contrast, genes involved in glucose and lipid metabolism showed differential expression. In conclusion, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby, a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks. Full article