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

Jan 4, 2021Chronobiology international

Sex differences in daily melatonin and body clock protein patterns in obese Neotomodon alstoni mice

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Abstract

Obese male mice exhibit an absent 24-hour rhythm of the PER1 protein across all tissues.

Circadian dysfunction may contribute to obesity, with distinct effects observed between sexes.
Obese mice show reduced locomotor activity compared to their lean counterparts.
Lean and obese mice exhibit differences in the expression of PER1 and BMAL1 proteins in a sex-linked manner.
Significant rhythms of PER1 and BMAL1 are present in obese females but absent in obese males.
Obese mice do not display a rhythmic pattern of circulating serum melatonin, which differs between sexes.
Obese male mice have lower melatonin levels compared to lean males, while obese females have higher levels than lean females.

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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. Themouse is a suitable model for such research. This study employedmice 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 obeseadult 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 inis 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. Neotomodon alstoni N. alstoni N. alstoni N. alstoni

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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

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