Removal of melatonin receptor type 1 signalling induces dyslipidaemia and hormonal changes in mice subjected to environmental circadian disruption

Background: Melatonin is a hormone secreted by the pineal gland in a circadian rhythmic manner with peak synthesis at night. Melatonin signalling was suggested to play a critical role in metabolism during the circadian disruption.

Methods: Melatonin-proficient (C3H-f^+/+ or WT) and melatonin receptor type 1 knockout (MT₁ KO) male and female mice were phase-advanced (6 hours) once a week for 6 weeks. Every week, we measured weight, food intake and basal glucose levels. At the end of the experiment, we sacrificed the animals and measured the blood's plasma for lipids profile (total lipids, phospholipids, triglycerides and total cholesterol), metabolic hormones profiles (ghrelin, leptin, insulin, glucagon, glucagon-like-peptide and resistin) and the body composition.

Results: Environmental circadian disruption (ECD) did not produce any significant effects in C3H-f^+/+, while it increased lipids profile in MT₁ KO with the significant increase observed in total lipids and triglycerides. For metabolic hormones profile, ECD decreased plasma ghrelin and increased plasma insulin in MT₁ KO females. Under control condition, MT₁ KO females have significantly different body weight, fat mass, total lipids and total cholesterol than the control C3H-f^+/+ females.

Conclusion: Our data show that melatonin-proficient mice are not affected by ECD. When the MT₁ receptors are removed, ECD induced dyslipidaemia in males and females with females experiencing the most adverse effect. Overall, our data demonstrate that MT₁ signalling is an essential modulator of lipid and metabolic homeostasis during ECD.