bims-ciryme 2022-07-10 papers

Cell Rep. 2022 Jul 05. pii: S2211-1247(22)00797-5. [Epub ahead of print]40(1): 111008

Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome.

Ana Carolina Dantas Machado, Steven D Brown, Amulya Lingaraju, Vignesh Sivaganesh, Cameron Martino, Amandine Chaix, Peng Zhao, Antonio F M Pinto, Max W Chang, R Alexander Richter, Alan Saghatelian, Alan R Saltiel, Rob Knight, Satchidananda Panda, Amir Zarrinpar.

Compositional oscillations of the gut microbiome are essential for normal peripheral circadian rhythms, both of which are disrupted in diet-induced obesity (DIO). Although time-restricted feeding (TRF) maintains circadian synchrony and protects against DIO, its impact on the dynamics of the cecal gut microbiome is modest. Thus, other regions of the gut, particularly the ileum, the nexus for incretin and bile acid signaling, may play an important role in entraining peripheral circadian rhythms. We demonstrate the effect of diet and feeding rhythms on the ileal microbiome composition and transcriptome in mice. The dynamic rhythms of ileal microbiome composition and transcriptome are dampened in DIO. TRF partially restores diurnal rhythms of the ileal microbiome and transcriptome, increases GLP-1 release, and alters the ileal bile acid pool and farnesoid X receptor (FXR) signaling, which could explain how TRF exerts its metabolic benefits. Finally, we provide a web resource for exploration of ileal microbiome and transcriptome circadian data.

Keywords: 16S; CP: Microbiology; FXR; RNA-seq; bile acids; incretins; lumen; microbiota; small intestine

DOI: https://doi.org/10.1016/j.celrep.2022.111008

Eur J Neurosci. 2022 Jul 07.

Electrophysiological complexity in the rat dorsomedial hypothalamus and its susceptibility to daily rhythms and high-fat diet.

Anna Magdalena Sanetra, Katarzyna Palus-Chramiec, Lukasz Chrobok, Marian Henryk Lewandowski.

The Dorsomedial Hypothalamus (DMH) in amongst the most important brain structures involved in the regulation of feeding behaviour and metabolism. In contrast to other hypothalamic centres, its main role is related to the circadian rhythmicity of food intake and energy homeostasis; both reported to be disrupted in obesity. In modern world, overweight and obesity reached global epidemic proportions. Thus, not only is it important to study their negative implications, but also the mechanism responsible for their development. Here we exposed rats to short-term (2-4 weeks) high-fat diet (HFD) - not long enough to induce obesity. Next, we performed electrophysiological patch-clamp recordings ex vivo from neurons in the DMH either during the day or at night. Our results showed a day-to-night change in the firing frequency of DMH cells, with higher activity during the dark phase. This was abolished by HFD consumption, resulting in a decreased threshold for action potential generation during the day and therefore increased electrical activity at this phase. We propose this electrophysiological disturbances as a mechanism for the induction of abnormal daytime feeding, previously observed for HFD-fed animals, which might in turn contribute to the development of obesity. In addition, we provide an electrophysiological characteristic of DMH neurons with a separation into three anatomically and functionally distinct subpopulations, namely the compact part, separating the structure into the ventral and dorsal divisions. Our study is the first to show electrophysiological complexity of the DMH with its sensitivity to diet and daily rhythms.

Keywords: chronobiology; food intake; metabolism; obesity; patch-clamp

DOI: https://doi.org/10.1111/ejn.15759

Anim Cells Syst (Seoul). 2022 ;26(3): 92-98

Leptin-inhibited neurons in the lateral parabrachial nucleus do not alter food intake or glucose balance.

Seahyung Park, Kevin W Williams, Jong-Woo Sohn.

The lateral parabrachial nucleus (LPBN) has been shown to be involved in the suppression of appetite at the pharmacological, optogenetic and chemogenetic levels. However, the signalling that mediates activation of these neurons in physiological conditions has been hindered by difficulties in segregating different cell populations in this region. Using reporter mice, we identify at the electrophysiological level the effects of an anorexic hormone, leptin, on leptin receptor (ObR)-expressing neurons in the LPBN (LPBNObR neurons). Application of leptin caused inhibition in a subpopulation of LPBNObR neurons. This effect was mediated by an increased potassium conductance and was also accompanied by a decrease in excitatory synaptic input onto these neurons. However, mimicking the inhibitory effects of leptin on LPBNObR neurons through chemogenetics led to no changes in feeding or glucose levels, which suggests that leptin action on LPBNObR neurons may not be sufficient to regulate these metabolic aspects.

Keywords: Appetite; chemogenetics; glucose; leptin; parabrachial nucleus

DOI: https://doi.org/10.1080/19768354.2022.2084159

Neurosci Lett. 2022 Jul 04. pii: S0304-3940(22)00333-0. [Epub ahead of print] 136772

The impact of lithium on circadian rhythms and implications for bipolar disorder pharmacotherapy.

Kayla E Rohr, Michael J McCarthy.

Bipolar disorder (BD) is characterized by disrupted circadian rhythms affecting sleep, arousal, and mood. Lithium is among the most effective mood stabilizer treatments for BD, and in addition to improving mood symptoms, stabilizes sleep and activity rhythms in treatment responsive patients. Across a variety of experimental models, lithium has effects on circadian rhythms. However, uncertainty exists as to whether these actions directly pertain to lithium's therapeutic effects. Here, we consider evidence from mechanistic studies in animals and cells and clinical trials in BD patients that identify associations between circadian rhythms and the therapeutic effects of lithium. Most evidence indicates that lithium has effects on cellular circadian rhythms and increases morningness behaviors in BD patients, changes that may contribute to the therapeutic effects of lithium. However, much of this evidence is limited by cross-sectional analyses and/or imprecise proxy markers of clinical outcomes and circadian rhythms in BD patients, while mechanistic studies rely on inference from animals or small numbers of patient samples. Further study may clarify the essential mechanisms underlying lithium responsive BD, better characterize the longitudinal changes in circadian rhythms in BD patients and inform the development of therapeutic interventions targeting circadian rhythms.

Keywords: animal models; bipolar disorder; chronotype; circadian rhythms; gene expression; lithium; neurons

DOI: https://doi.org/10.1016/j.neulet.2022.136772