bims-ciryme 2022-03-06 papers

Proc Natl Acad Sci U S A. 2022 Mar 08. 119(10): e2200083119

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease.

Céline Jouffe, Benjamin D Weger, Eva Martin, Florian Atger, Meltem Weger, Cédric Gobet, Divya Ramnath, Aline Charpagne, Delphine Morin-Rivron, Elizabeth E Powell, Matthew J Sweet, Mojgan Masoodi, N Henriette Uhlenhaut, Frédéric Gachon.

SignificanceWhile increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.

Keywords: circadian clock; estrogen; growth hormone; insulin resistance; nonalcoholic fatty liver disease

DOI: https://doi.org/10.1073/pnas.2200083119

Eur J Neurosci. 2022 Mar 01.

Deviant circadian rhythmicity, corticosterone variability and trait testosterone levels in aggressive mice.

F Mogavero, K van Zwieten, J K Buitelaar, J C Glennon, M J A G Henckens.

Although aggression has been linked to disturbances of circadian rhythm, insight into the neural substrate of this association is currently lacking. The suprachiasmatic nucleus (SCN) of the hypothalamus, the master circadian clock, is regulated by clock genes and known to influence the secretion of cortisosterone and testosterone, important hormones implicated in aggression. Here, we investigated deviations in the regulation of the locomotor circadian rhythm and hormonal levels in a mouse model of abnormal aggression. We tested aggressive BALB/cJ and control BALB/cByJ mice in the resident-intruder paradigm and compared them on their locomotor circadian rhythm during a 12h light/12h dark cycle and constant darkness. State (serum) corticosterone and trait (hair) corticosterone and testosterone levels were determined, and immunohistochemistry was performed to assess the expression of important clock proteins, PER1 and PER2, in the core and shell of the SCN at the start of their active phase. Compared to BALB/cByJ mice, aggressive BALB/cJ mice displayed: 1) a shorter free-running period in constant darkness; 2) reduced state corticosterone variability between circadian peak and trough, but no differences in corticosterone trait levels; 3) lower testosterone trait levels; 4) higher PER1 expression in the SCN shell with no changes in PER2 in either SCN subregion during the early dark phase. Together, these results suggest that aggressive BALB/cJ mice have disturbances in different components encompassing the circadian and hormonal cycle, emphasizing their value for future investigation of the causal relationship between SCN function, circadian clocks and aggression.

Keywords: Aggression; Circadian rhythms; Clock; Corticosterone; Suprachiasmatic nucleus; Testosterone

DOI: https://doi.org/10.1111/ejn.15632

BMJ Open Diabetes Res Care. 2022 Mar;pii: e002632. [Epub ahead of print]10(2):

Rest-activity circadian rhythm and impaired glucose tolerance in adults: an analysis of NHANES 2011-2014.

Yanyan Xu, Shaoyong Su, William V McCall, Carlos Isales, Harold Snieder, Xiaoling Wang.

INTRODUCTION: Circadian rhythm disturbance occurs in type 2 diabetes, yet it is unknown whether it also exists in the prediagnostic phase of the disease. Thus, we examined the association of rest-activity circadian rhythm with 2-hour glucose levels and the risk of impaired glucose tolerance (IGT) in a nationally representative sample of adults without diabetes using a cross-sectional design.
RESEARCH DESIGN AND METHODS: We analyzed data from 2760 adults without diabetes (age ≥20) with at least 4 days of validated accelerometer recordings and a valid oral glucose tolerance test from the National Health and Nutrition Examination Survey 2011-2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings.
RESULTS: In the models adjusting for multiple covariates, a one-quantile increase in relative amplitude (ie, increased circadian rhythmicity) was associated with 2.66 mg/dL decrease in 2-hour glucose level (95% CI -3.94 to -1.38, p<0.001) and a decreased odds of IGT (OR 0.75, 95% CI 0.63 to 0.89, p=0.002). A one-quantile increase in intradaily variability (ie, increased rhythm fragmentation) was associated with 3.01 mg/dL increase in 2-hour glucose level (95% CI 1.52 to 4.49, p=0.001) and an increased odds of IGT (OR 1.37, 95% CI 1.19 to 1.58, p<0.001).
CONCLUSIONS: Circadian disruption is significantly associated with impaired glucose homeostasis in a general population of adults without diabetes. The association of circadian rhythm abnormalities with indicators of the pre-diabetic state suggests that circadian dysfunction may contribute to early disease pathogenesis.

Keywords: circadian rhythm; diabetes mellitus, type 2; glucose tolerance test

DOI: https://doi.org/10.1136/bmjdrc-2021-002632

Curr Biol. 2022 Feb 28. pii: S0960-9822(22)00049-5. [Epub ahead of print]32(4): R173-R176

Glycemic control: Tanycytes march to the beat of the suprachiasmatic drummer.

Monica Imbernon, Benedicte Dehouck, Vincent Prevot.

The suprachiasmatic nucleus (SCN) synchronizes physiology with the individual's environment to optimize bodily functions. A new study reveals that tanycytes follow the tempo set by the SCN to effect circadian changes in both brain entry of blood glucose and glycemia.

DOI: https://doi.org/10.1016/j.cub.2022.01.038