bims-ciryme 2023-02-12 papers

Mol Metab. 2023 Feb 04. pii: S2212-8778(23)00025-X. [Epub ahead of print] 101691

Rest phase snacking increases energy resorption and weight gain in male mice.

Kimberly Begemann, Isabel Heyde, Pia Witt, Julica Inderhees, Brinja Leinweber, Christiane E Koch, Olaf Jöhren, Rebecca Oelkrug, Arkadiusz Liskiewicz, Timo D Müller, Henrik Oster.

OBJECTIVE: Snacking, i.e., the intake of small amounts of palatable food items, is a common behavior in modern societies, promoting overeating and obesity. Shifting food intake into the daily rest phase disrupts circadian rhythms and is also known to stimulate weight gain. We therefore hypothesized that chronic snacking in the inactive phase may promote body weight gain and that this effect is based on disruption of circadian clocks.
METHODS: Male mice were fed a daily chocolate snack either during their rest or their active phase and body weight development and metabolic parameters were investigated. Snacking experiments were repeated in constant darkness and in clock-deficient mutant mice to examine the role of external and internal time cues in mediating the metabolic effects of snacking.
RESULTS: Chronic snacking in the rest phase increased body weight gain and disrupted metabolic circadian rhythms in energy expenditure, body temperature, and locomotor activity. Additionally, these rest phase snacking mice assimilated more energy during the inactive phase. Body weight remained increased in rest phase snacking wildtype mice in constant darkness as well as in clock-deficient mutant mice under a regular light-dark cycle compared to mice snacking in the active phase. Weight gain effects were abolished in clock-deficient mice in constant darkness.
CONCLUSIONS: Our data suggest that mistimed snacking increases energy resorption and promotes body weight gain. This effect requires a functional circadian clock at least under constant darkness conditions.

Keywords: body weight gain; circadian clock; energy intake; energy resorption; light-dark cycle; snacking

DOI: https://doi.org/10.1016/j.molmet.2023.101691

Cell Rep. 2023 Feb 06. pii: S2211-1247(23)00050-5. [Epub ahead of print]42(2): 112039

Circadian regulation of dentate gyrus excitability mediated by G-protein signaling.

Jose Carlos Gonzalez, Haeun Lee, Angela M Vincent, Angela L Hill, Lacy K Goode, Gwendalyn D King, Karen L Gamble, Jacques I Wadiche, Linda Overstreet-Wadiche.

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium currents that reduce excitability during the Light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the Light phase by removing G-protein regulation. These results reveal that circadian transcriptional machinery regulates intrinsic excitability by coordinated regulation of ion channels by G-protein signaling, highlighting a potential novel mechanism of cell-autonomous oscillations.

Keywords: Bmal1; CP: Neuroscience; G-protein; GIRK; NALCN; circadian rhythms; dentate gyrus; excitability; granule cell; intrinsic properties

DOI: https://doi.org/10.1016/j.celrep.2023.112039

PNAS Nexus. 2022 Jul;1(3): pgac112

Nested calcium dynamics support daily cell unity and diversity in the suprachiasmatic nuclei of free-behaving mice.

Lama El Cheikh Hussein, Pierre Fontanaud, Patrice Mollard, Xavier Bonnefont.

The suprachiasmatic nuclei (SCN) of the anterior hypothalamus host the circadian pacemaker that synchronizes mammalian rhythms with the day-night cycle. SCN neurons are intrinsically rhythmic, thanks to a conserved cell-autonomous clock mechanism. In addition, circuit-level emergent properties confer a unique degree of precision and robustness to SCN neuronal rhythmicity. However, the multicellular functional organization of the SCN is not yet fully understood. Indeed, although SCN neurons are well-coordinated, experimental evidences indicate that some neurons oscillate out of phase in SCN explants, and possibly to a larger extent in vivo. Here, to tackle this issue we used microendoscopic Ca2+ i imaging and investigated SCN rhythmicity at a single cell resolution in free-behaving mice. We found that SCN neurons in vivo exhibited fast Ca2+ i spikes superimposed upon slow changes in baseline Ca2+ i levels. Both spikes and baseline followed a time-of-day modulation in many neurons, but independently from each other. Daily rhythms in basal Ca2+ i were highly coordinated, while spike activity from the same neurons peaked at multiple times of the light cycle, and unveiled clock-independent coactivity in neuron subsets. Hence, fast Ca2+ i spikes and slow changes in baseline Ca2+ i levels highlighted how multiple individual activity patterns could articulate within the temporal unity of the SCN cell network in vivo, and provided support for a multiplex neuronal code in the circadian pacemaker.

Keywords: calcium signaling; circadian rhythms; in vivo imaging

DOI: https://doi.org/10.1093/pnasnexus/pgac112

Diabetes Res Clin Pract. 2023 Feb 02. pii: S0168-8227(23)00044-X. [Epub ahead of print] 110569

Time-restricted eating improves measures of daily glycaemic control in people with type 2 diabetes.

Evelyn B Parr, Nikolai Steventon-Lorenzen, Richard Johnston, Nirav Maniar, Brooke L Devlin, Karen H C Lim, John A Hawley.

AIMS: Examine the effect of 5 d/wk., 9-h time-restricted eating (TRE) protocol on 24-h glycaemic control in adults with type 2 diabetes (T2D).
METHODS: Nineteen adults with T2D (10 F/9 M; 50 ± 9 y, HbA1c 7.6%(60 mmol/mol), BMI ~34 kg/m2) completed a pre-post non-randomised trial comprising of a 2-wk Habitual monitoring period followed by 9-h (10:00-19:00 h) TRE for 4-wk. Glycaemic control was assessed via continuous glucose monitoring (CGM; for mean 24-h glucose concentrations, 24-h total area under the curve (AUC) and glucose variability metrics), with dietary records and physical activity monitoring. Changes in CGM measures, dietary intake and physical activity were assessed with linear mixed-effects models.
RESULTS: TRE did not alter dietary energy intake, macronutrient composition or physical activity, but reduced the daily eating window (-2 h 35 min, P < 0.001). Compared to the Habitual period, 24-h glucose concentrations (mean, SD) and AUC decreased in the 4-wk TRE period (mean:-0.7 ± 1.2 mmol/L, P = 0.02; SD:-0.2 ± 0.3 mmol/L, P = 0.01; 24-h AUC:-0.9 ± 1.4 mmol/L⋅h-1 P = 0.01). During TRE, participants spent 10% more time in range (3.9-10.0 mmol/L; P = 0.02) and 10% less time above range (>10.0 mmol/L; P = 0.02).
CONCLUSIONS: Adhering 5 d/wk. to 9-h TRE improved glycaemic control in adults with T2D, independent of changes in physical activity or dietary intake.
CLINICAL TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12618000938202.

Keywords: Continuous glucose monitoring; Diet; Glucose variability; Nutrition; Physical activity

DOI: https://doi.org/10.1016/j.diabres.2023.110569