Obese Neotomodon alstoni mice exhibit sexual dimorphism in the daily profile of circulating melatonin and clock proteins PER1 and BMAL1 in the hypothalamus and peripheral oscillators

ABSTRACT

Obesity is a global health threat and a risk factor for several metabolic conditions. Though circadian dysfunction has been considered among the multiple causes of obesity, little work has been done to explore the relationship between obesity, circadian dysfunction, and sexual dimorphism. The Neotomodon alstoni mouse is a suitable model for such research. This study employed N. alstoni mice in a chronobiological analysis to determine whether there is circadian desynchronization of relative PER1 and BMAL1 protein levels in the hypothalamus, liver, visceral white adipose tissue, kidney, and heart. It also compared differences between sexes and lean and obese N. alstoni adult mice, by recording behavior and daily circulating serum melatonin as markers of circadian output. We found that obese mice display reduced locomotor activity. Additionally, Cosinor analyses of the relative expression of PER1 and BMAL1 show differences between lean and obese mice in a sex-linked manner. The PER1 24 h rhythm was absent in all tissues of obese males and significant in the tissues of obese females. The BMAL1 24 h rhythm also was significant in most of the tissues tested in lean males, whereas it was significant and shifted the acrophase (peak time of rhythm) in most of the tissues in obese females. Both lean male and female mice showed a rhythmic 24 h pattern of circulating serum melatonin. This daily profile was not only absent in obese mice of both sexes but showed sexual dimorphism. Obese male mice showed lower circulating levels of melatonin compared to lean male mice, but they were higher in obese females compared to lean females. Our results suggest that obesity in N. alstoni is associated with an internal circadian desynchronization in a sex-dependent manner. Overall, this study reinforces the need for further research on the neuroendocrinology of obesity and circadian rhythms using this biological model.

KEYWORDS:

• Obesity
• melatonin
• chronodisruption
• sex differences
• Neotomodon alstoni mice
• circadian rhythm
• BMAL1
• PER1

Acknowledgements

Arellanes-Licea EC was funded by Dirección General de Asuntos del Personal Académico (DGAPA), UNAM postdoctoral fellowship program. This work was supported by PAPIIT, UNAM research grant IN200620, and UMDI-104419 to MM-A. We thank Dr. Julieta Berenice Rivera-Zavala for her skillful technical assistance and M.Sc. Teresa Bosques-Tistler and editors for English review and academic editing.

Disclosure statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Suppelementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the Universidad Nacional Autónoma de México, DGAPA. [DGAPA Postdoctoral Fellowship to ECAL, and PAPIIT IN200620 to MMA]; Facultad de Ciencias UNAM [UMDI104419].