The circadian clock of the body controls the timing of key physiological processes. It’s influenced by environmental cues, like day and night cycles, as well as nutrient status. The past decade of research has led to a growing body of evidence that disruption of the circadian clock, such as that seen in shift workers, plays a critical role in the development of cardiometabolic syndrome (CMS).

CMS is defined as a set of metabolic abnormalities, including obesity, blood-lipid accumulation, insulin resistance and high blood-pressure. CMS leads to changes in heart structure and function, which increase the risk of heart failure, with higher prevalence in women. (In fact, heart disease is the leading cause of death in women and is responsible for one in every five female deaths, although more research needs to be done to learn why women are at greater risk).

Furthermore, increasing evidence has shown that disrupted circadian rhythms, such as seen in shift workers, is closely associated with increased risk for CMS and worse outcomes. Shift workers are common in the modern world, accounting for 30 per cent of the work force. Therefore, there is an immediate need to reveal the molecular link between circadian disruption and CMS and to understand its sex-dependent underlying mechanisms.

CMS is a growing public healthcare issue worldwide due to its increasing prevalence and its extensive influence on various age, gender and ethnic groups. Moreover, since those diagnosed with CMS ultimately develop heart failure for which there is no cure, CMS is considered a major socioeconomic burden to our health care system since it requires costly long-term care. This impacts the quality of life of the patient as well as their family members who must provide care.

Therefore, this proposal will investigate the link between circadian disruption and cardiometabolic heart failure, with the goal of minimizing heart disease. To do this, we’ll apply a “night shift-work model” on male and female CMS mice.

We’ll then examine a nutritional stimulation approach that involves modulating the expression of genes that control both circadian regulation and heart response during CMS.

We anticipate that this study will promote new therapeutic avenues that will improve the metabolic damage caused by circadian disruption. This research will contribute to the improved health of Canadians and lessen the burden on our health system.