Circadian disruption by short light exposure and a high energy diet impairs glucose tolerance and increases cardiac fibrosis in Psammomys obesus

Victoria A Nankivell,Alex Brown,Peter J Psaltis,Paul Zimmet,Noga Kronfeld-Schor,Stephen J Nicholls,Joanne T M Tan,Carmel Bilu,Kaitlin R Morrison,Laura A Wilsdon,Christina A Bursill

doi:10.1038/s41598-021-89191-7

Abstract

Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis. We sought to determine the impact of circadian disruption on the induction of hyperglycaemia, inflammation and cardiac fibrosis. Methods: Psammomys obesus (P. obesus) were exposed to neutral (12 h light:12 h dark) or short (5 h light:19 h dark) photoperiods and fed a low energy (LE) or high energy (HE) diet for 8 or 20 weeks. To determine daily rhythmicity, P. obesus were euthanised at 2, 8, 14, and 20 h after ‘lights on’. Results: P. obesus exposed to a short photoperiod for 8 and 20 weeks had impaired glucose tolerance following oral glucose tolerance testing, compared to a neutral photoperiod exposure. This occurred with both LE and HE diets but was more pronounced with the HE diet. Short photoperiod exposure also increased myocardial perivascular fibrosis after 20 weeks on LE (51%, P < 0.05) and HE (44%, P < 0.05) diets, when compared to groups with neutral photoperiod exposure. Short photoperiod exposure caused elevations in mRNA levels of hypertrophy gene Nppa (atrial natriuretic peptide) and hypertrophy transcription factors Gata4 and Mef2c in myocardial tissue after 8 weeks. Conclusion: Exposure to a short photoperiod causes impaired glucose tolerance in P. obesus that is exacerbated with HE diet and is accompanied by an induction in myocardial perivascular fibrosis.

Highlights

Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis
Glucose tolerance was impaired in groups that were exposed to a high energy (HE) diet or short photoperiod or both (12:12HE, 5:19LE and 5:19HE groups)
Glucose tolerance was impaired in groups that were exposed to a short photoperiod (5:19LE and 5:19HE groups) as glucose levels were significantly elevated 120 min after glucose infusions, compared to corresponding 0 min timepoints (Fig. 1b, P < 0.05 for all)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis. Disruptions to the circadian system have been shown to have a range of negative health impacts including increased inflammation, impaired glucose regulation, elevated risks of obesity, cardiovascular disease, metabolic syndrome, and T 2DM13–19. A unique rodent model, the gerbil Psammomys obesus (P. obesus), is diurnal and spontaneously develops diet induced obesity and T2DM when fed a typical laboratory rodent d iet[21,22,23] This has significant advantages over the streptozotocin infusion model that causes destruction of pancreatic beta cells and more closely mimics Type 1 DM20. This study sought to determine the effect that a typical “westernised” shift worker lifestyle with high energy diet and disrupted circadian cycle on the development of T2DM, cardiac fibrosis and inflammation. Using the unique pathophysiologically relevant P. obesus model, we simulated this scenario using a rodent chow and exposure to a short photoperiod for either 8 or 20 weeks

Methods

Results

Conclusion