In mammals, an endogenous clock located in the suprachiasmatic nucleus (SCN), synchronizes physiological and biological rhythms to the environmental light–dark cycle. In experiments, most... Show moreIn mammals, an endogenous clock located in the suprachiasmatic nucleus (SCN), synchronizes physiological and biological rhythms to the environmental light–dark cycle. In experiments, most researchers applied rectangular scheme as the external light–dark scheme received by the SCN neuronal oscillators. However, the external light intensity changes gradually throughout the day. Therefore, trapezoidal schemes (twilight) or sinusoidal schemes were also applied. Thus far, the effects of different light–dark schemes on the oscillators of the SCN did not get fully explored. In the present study, we theoretically analyzed how the five common light–dark schemes affect the entrainment ability of the SCN, based on a Poincaré model. We numerically found that when the maximum light intensity, the minimum light intensity, and the total amount of light exposure per cycle were the same, the largest entrainment range was obtained in the oscillators receiving more light in the daytime. However if, under the condition of 12:12-h illumination, the total amount of light exposure per cycle was the same, the maximum light intensity during the day leaded to an increased range of entrainment. Moreover, the entrainment range was reduced when the photoperiod was extended. Note that, increasing the maximum light intensity increased the entrainment ability of all light–dark schemes. Our results exposes the important role of light–dark schemes in the entrainment ability of the SCN network, and provides a potential explanation for the diversity of the entrainment range between diurnal and nocturnal animals. Show less
Aims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing... Show moreAims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with type 2 diabetes. In this study we aimed to identify key disturbances in the diurnal rhythms of the white adipose tissue transcriptome in obese individuals with type 2 diabetes.MethodsIn a case-control design, we included six obese individuals with type 2 diabetes and six healthy, lean control individuals. All participants were provided with three identical meals per day for 3days at zeitgeber time (ZT, with ZT 0:00 representing the time of lights on) 0:30, 6:00 and 11:30. Four sequential subcutaneous abdominal adipose tissue samples were obtained, on day 2 at ZT 15:30, and on day 3 at ZT 0:15, ZT 5:45 and ZT 11:15. Gene expression was measured using RNA sequencing.ResultsThe core clock genes showed reduced amplitude oscillations in the individuals with type 2 diabetes compared with the healthy control individuals. Moreover, in individuals with type 2 diabetes, only 1.8% (303 genes) of 16,818 expressed genes showed significant diurnal rhythmicity, compared with 8.4% (1421 genes) in healthy control individuals. Enrichment analysis revealed a loss of rhythm in individuals with type 2 diabetes of canonical metabolic pathways involved in the regulation of lipolysis. Enrichment analysis of genes with an altered mesor in individuals with type 2 diabetes showed decreased activity of the translation initiating pathway EIF2 signaling'. Individuals with type 2 diabetes showed a reduced diurnal rhythm in postprandial glucose concentrations.Conclusions/interpretationDiurnal clock and metabolic gene expression rhythms are decreased in subcutaneous adipose tissue of obese individuals with type 2 diabetes compared with lean control participants. Future investigation is needed to explore potential treatment targets as identified by our study, including clock enhancement and induction of EIF2 signalling.Data availabilityThe raw sequencing data and supplementary files for rhythmic expression analysis and Ingenuity Pathway Analysis have been deposited in NCBI Gene Expression Omnibus (GEO series accession number GSE104674). Show less
