bims-ciryme 2019-11-10 papers

Proc Natl Acad Sci U S A. 2019 Nov 04. pii: 201914003. [Epub ahead of print]

Sex differences in the circadian misalignment effects on energy regulation.

Jingyi Qian, Christopher J Morris, Rosanna Caputo, Wei Wang, Marta Garaulet, Frank A J L Scheer.

Shift work causes circadian misalignment and is a risk factor for obesity. While some characteristics of the human circadian system and energy metabolism differ between males and females, little is known about whether sex modulates circadian misalignment effects on energy homeostasis. Here we show-using a randomized cross-over design with two 8-d laboratory protocols in 14 young healthy adults (6 females)-that circadian misalignment has sex-specific influences on energy homeostasis independent of behavioral/environmental factors. First, circadian misalignment affected 24-h average levels of the satiety hormone leptin sex-dependently (P < 0.0001), with a ∼7% decrease in females (P < 0.05) and an ∼11% increase in males (P < 0.0001). Consistently, circadian misalignment also increased the hunger hormone ghrelin by ∼8% during wake periods in females (P < 0.05) without significant effect in males. Females reported reduced fullness, consistent with their appetite hormone changes. However, males reported a rise in cravings for energy-dense and savory foods not consistent with their homeostatic hormonal changes, suggesting involvement of hedonic appetite pathways in males. Moreover, there were significant sex-dependent effects of circadian misalignment on respiratory quotient (P < 0.01), with significantly reduced values (P < 0.01) in females when misaligned, and again no significant effects in males, without sex-dependent effects on energy expenditure. Changes in sleep, thermoregulation, behavioral activity, lipids, and catecholamine levels were also assessed. These findings demonstrate that sex modulates the effects of circadian misalignment on energy metabolism, indicating possible sex-specific mechanisms and countermeasures for obesity in male and female shift workers.

Keywords: appetite; circadian disruption; energy metabolism; sex difference; shift work

DOI: https://doi.org/10.1073/pnas.1914003116

Neuroscience. 2019 Oct 31. pii: S0306-4522(19)30688-8. [Epub ahead of print]

Diurnal Regulation of the Orexin/Hypocretin System in Mice.

Kathrin Ventzke, Henrik Oster, Olaf Jöhren.

A prominent feature of the hypothalamic neuropeptides orexins/hypocretins is their role in the regulation of sleep-wake behavior. While there is strong evidence for a diurnal (i.e. 24-h) rhythmicity of the expression of prepro-orexin (PPO) and its cleavage products, orexin A and B, it is not known whether orexin receptors are also subject to diurnal regulation. Here we ask whether besides the regulation of PPO the expression of the orexin receptor subtypes OX1R and OX2R varies over 24 hours in the mouse brain. The mRNA levels of PPO, OX1R, and OX2R as well as of various clock genes were analyzed over 24 hours in the hypothalamus, cortex, and adrenal glands of male mice using qPCR. We found a significant diurnal regulation of the mRNA levels of PPO as well as both orexin receptor subtypes in the brain, while no regulation was observed in adrenal glands. While in the cortex the mRNA levels of both OX1R and OX2R showed a significant diurnal regulation, in the hypothalamus, only the OX2R mRNA expression was subject to a diurnal rhythm. The expression of both orexin receptor subtypes significantly correlated with that of clock genes. Remarkably, the expression pattern of OX2R showed a strong and highly significant correlation with that of the clock gene Bmal1 in the cortex and hypothalamus. These results suggest that the rhythmic expression of orexin receptors is linked to clock gene expression and that OX2R may potentially play a role in the timing of sleep-wake behavior.

Keywords: OX(1)R; OX(2)R; diurnal expression; hypothalamus; orexin receptor subtypes

DOI: https://doi.org/10.1016/j.neuroscience.2019.10.002

Trends Endocrinol Metab. 2019 Oct 30. pii: S1043-2760(19)30180-8. [Epub ahead of print]

Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism.

Katya Frazier, Eugene B Chang.

The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiology and metabolism. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and bile acids (BAs). Key gaps in knowledge and major challenges that remain in the circadian and microbiome fields are also discussed, including animal versus human models and the need for precise timed sample collection.

Keywords: bile acids; circadian rhythms; metabolism; microbiome; short-chain fatty acids

DOI: https://doi.org/10.1016/j.tem.2019.08.013