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Essential for survival and reproduction, the circadian timing system (CTS) regulates adaptation to cyclical changes such as the light/dark cycle, temperature change, and food availability. The regulation of energy homeostasis possesses rhythmic properties that correspond to constantly fluctuating needs for energy production and consumption. Adipose tissue is mainly responsible for energy storage and, thus, operates as one of the principal components of energy homeostasis regulation. In accordance with its roles in energy homeostasis, alterations in adipose tissue’s physiological processes are associated with numerous pathologies, such as obesity and type 2 diabetes. These alterations also include changes in circadian rhythm. In the current review, we aim to summarize the current knowledge regarding the circadian rhythmicity of adipogenesis, lipolysis, adipokine secretion, browning, and non-shivering thermogenesis in adipose tissue and to evaluate possible links between those alterations and metabolic diseases. Based on this evaluation, potential therapeutic approaches, as well as clock genes as potential therapeutic targets, are also discussed in the context of chronotherapy.

Statins are known to display benefits in various diseases independently from their cholesterol lowering properties. In this study, we investigated the acute effects of atorvastatin on vascular reactivity to various spasmogens in isolated rat aorta. The responses to noradrenaline (NA, 10(-8) -10(-4) m), endothelin-1 (ET-1, 10(-10) -10(-7) m), and potassium chloride (KCl, 10-100 mm) were evaluated in aortic rings pretreated with atorvastatin (10(-7) -10(-4) m, 30 min). To verify the mechanism of action, the effects of atorvastatin were studied in the presence of cholesterol precursor, mevalonate (10(-2) m, 45 min), mevalonate-derived isoprenoids, namely geranylgeranyl pyrophosphate (GGPP, 5 × 10(-6) m, 30 min) and farnesyl pyrophosphate (FPP, 5 × 10(-6) m, 30 min), and in the absence of endothelium. In parallel, aortic rings were pretreated with the specific inhibitor of Rho kinase, Y-27632 (10(-7) -10(-6) m). Atorvastatin significantly and concentration-dependently reduced the contractions to spasmogens in rat aorta. This acute inhibitory effect was also evident in endothelium-denuded rings. Pretreatment with mevalonate and GGPP, but not with FPP, reversed the inhibitory effect of atorvastatin (10(-4) m) on NA and ET-1 induced contractions. Similar to atorvastatin, pretreatment with Y-27632 inhibited the contractions to NA and KCl in a concentration-dependent manner. Western blot analysis revealed that both atorvastatin (10(-4) m) and Y-27632 (10(-6) m) pretreatment inhibited the phosphorylation of myosin phosphatase target subunit-1 (MYPT-1) triggered by NA, indicating an inhibitory influence on myosin phosphatase. In conclusion, atorvastatin displayed an acute inhibitory effect on vascular contractility evoked by various spasmogens and the inhibitory effect was possibly mediated by the inhibition of mevalonate and GGPP synthesis as well as the prevention of MYPT-1 phosphorylation induced by Rho/Rho kinase.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which is characterized by persistent deficits in social communication and social interaction, limitations and deviations in verbal and nonverbal skills, repetitive patterns of behavior, interests or activities. The worldwide prevalence of ASD has been steadily increasing in recent decades. In 2016, the USA National Health Center for Health Statistics reported that ASD could be found in 1 out of 36 children (Christensen et al. 2016; Sharma et al. 2018). Due to the large variation in deficiencies and the deviations in symptoms between patients, the diagnosis of ASD can be quite difficult. Therefore, it is necessary to distinguish ASD from other neuropsychiatric disorders, and use appropriate evaluation methods to diagnose correctly in order to improve the clinical management of the disease (National Institute of Mental Health 2018; Baumer and Spence 2018).Recent studies have shown that multiple genetic factors play a role in the development of ASD (Lovato 2019). Siblings of ASD children also carry a higher risk of developing ASD (Bolton et al. 1994). It is reported that genetic and chromosomal abnormalities, such as Down's syndrome or fragile X syndrome, can be found in 10% of the children with ASD (DiGuiseppi et al. 2010; Hall et al. 2008). In addition, parental history of psychiatric disorders, premature birth and fetal exposure to psychotropic drugs, toxins, heavy metals and insecticides have been linked to the pathophysiology of ASD (Cattane et al. 2018; Sharma et al. 2018). With the emergence of possible etiologic causes, new therapy approaches may be introduced in the treatment of ASD (Emberti Gialloreti et al. 2019).