Forced internal desynchrony induces cardiometabolic alterations in adult rats

Abstract

Disruptions in circadian rhythms have been associated with several diseases, including cardiovascular and metabolic disorders. Forced internal desynchronization induced by a period of T-cycles of 22 h (T22 protocol) reaches the lower limit of entrainment and dissociates the circadian rhythmicity of the locomotor activity into two components, driven by different outputs from the suprachiasmatic nucleus (SCN). The main goal of this study was to evaluate the cardiovascular and metabolic response in rats submitted to internal desynchronization by T22 protocol. Male Wistar rats were assigned to either a control group subjected to a usual T-cycles of 24 h (12 h–12 h) or an experimental group subjected to the T22 protocol involving a 22-h symmetric light–dark cycle (11 h–11 h). After 8 weeks, rats subjected to the T22 exhibited desynchrony in their locomotor activity. Although plasma glucose and insulin levels were similar in both groups, desynchronized rats demonstrated dyslipidemia, significant hypertrophy of the fasciculate zone of the adrenal gland, low IRB, IRS2, PI3K, AKT, SOD and CAT protein expression and an increased expression of phosphoenolpyruvate carboxykinase in the liver. Furthermore, though they maintained normal baseline heart rates and mean arterial pressure levels, they also presented reduced baroreflex sensitivity. The findings indicate that circadian timing desynchrony following the T22 protocol can induce cardiometabolic disruptions. Early hepatic metabolism dysfunction can trigger other disorders, though additional studies are needed to clarify the causes.

Análise da qualidade de sono e da preferência diurna dos trabalhadores em turnos da área da saúde

“…A redução na qualidade e quantidade do sono estão associadas às queixas generalizadas de fadiga, ansiedade, depressão e aumento do neuroticismo 29 . Bem como, evidências crescentes de efeitos cardiovasculares adversos e possível aumento de distúrbios metabólicos relacionados [30][31][32] .…”

Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work

“…Overall, these studies show the role of MT in the restoration of the oxidative status in adipose tissue from obese animals. There are much fewer studies on the desynchronization of the circadian rhythm; however, a very comprehensive research study on the effects of forced internal desynchronization induced by a period of T-cycles of 22 h of male Wistar rats showed a significant decrease in HDL-cholesterol, a raise in LDL-cholesterol, a decrease in SOD and CAT protein expression and a reduction in baroreflex sensitivity [ 99 ]. This experiment indicates that cardio-metabolic impairment can be reproduced in rats and, indirectly confirms the experiments described above.…”

Different levels of circadian (de)synchrony ­– where does it hurt?

“…Thereby, mice predominantly utilize carbohydrates to fuel the body which hints to an impaired metabolic homeostasis ( West et al , 2017 ). Under 11:11 LD cycles, rats show dyslipidemia and lowered expression levels of proteins critical for insulin signaling as well as increased levels of enzymes involved in gluconeogenesis in liver indicating metabolic disruptions induced by forced desynchrony ( de Oliveira et al , 2019 ). Non-24-hour LD cycles result in abolished rhythmicity in heart rate and blood pressure ( Molcan and Zeman, 2017 ; West et al , 2017 ).…”