AIM: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle. METHODS: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling). RESULTS: CD attenuated the rhythmic output of the central clock in the suprachiasmatic nucleus via Prok2 signaling, thereby disrupting locomotor activity, the estrous cycle, sleep patterns, and mutual phase relationship between the central and peripheral clocks. In the periphery, CD abolished Per1,2 expression rhythms in peripheral tissues (liver, pancreas, colon) and worsened glucose homeostasis. In the liver, it impaired the expression of NAD+, lipid, and cholesterol metabolism genes and abolished most of the high-amplitude rhythms of lipids and polar metabolites. Interestingly, CD abolished the circadian rhythm of Cpt1a expression and increased the levels of long-chain acylcarnitines (ACar 18:2, ACar 16:0), indicating enhanced fatty acid oxidation in mitochondria. CONCLUSION: Our data show the widespread effects of CD on metabolism and point to ACars as biomarkers for CD due to misaligned sleep and feeding patterns.

• Keywords
• acylcarnitine, chronodisruption, clock, female, glucose homeostasis, liver, metabolome, pancreas, rat, sleep, suprachiasmatic nucleus,
• MeSH
• Circadian Clocks * physiology   MeSH
• Circadian Rhythm * physiology   MeSH
• Photoperiod MeSH
• Liver * metabolism   MeSH
• Carnitine * analogs & derivatives   metabolism   MeSH
• Rats MeSH
• Metabolome * physiology   MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• acylcarnitine MeSH Browser
• Carnitine * MeSH

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

• Keywords
• cardiovascular disease risk, circadian clock, circadian rhythm disruption, glucose tolerance, insulin sensitivity, time restricted eating, type 2 diabetes mellitus,
• MeSH
• Chronobiology Disorders physiopathology   complications   MeSH
• Circadian Rhythm * physiology   MeSH
• Diabetes Mellitus, Type 2 physiopathology   metabolism   MeSH
• Cardiovascular Diseases * etiology   physiopathology   MeSH
• Humans MeSH
• Metabolic Diseases * physiopathology   metabolism   etiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.

• MeSH
• Chronobiology Disorders physiopathology   metabolism   complications   MeSH
• Circadian Clocks physiology   MeSH
• Circadian Rhythm * physiology   MeSH
• Cardiovascular Diseases * metabolism   etiology   epidemiology   physiopathology   MeSH
• Humans MeSH
• Metabolic Diseases * metabolism   epidemiology   physiopathology   etiology   MeSH
• Disease Models, Animal MeSH
• Risk Factors MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH