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Interestingly, Npy1r mRNA expression was reduced in the ARC and in the paraventricular hypothalamic nuclei of female, but not male mice. check details These results demonstrated that female mice are resilient to hormonal and metabolic effects of limbic Npy1r gene inactivation, suggesting the existence of an estrogen-dependent relay necessary to ensure the maintenance of the homeostasis, that can be mediated by hypothalamic Y1R.Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β3-adrenergic receptor (β3-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that, in contrast to rodents, human BAT thermogenesis is not mediated by the stimulation of β3-AR. Oral administration of the β3-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to β1-AR and β2-AR, thereby increasing cardiovascular responses and white adipose tissue lipolysis, respectively. ADRB2 was co-expressed with UCP1 in human brown adipocytes. Pharmacological stimulation and inhibition of the β2-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through β2-AR signaling in humans (ClinicalTrials.govNCT02811289).Psychological stress has long been known to reduce adaptability to inflammatory challenges, although the precise mechanism has remained elusive. In a recent issue of Cell, Qing et al. (2020) demonstrate that psychological stress induces secretion of IL-6 from brown adipose tissue, which promotes hepatic gluconeogenesis, and reduces host fitness to inflammatory insults.The precise mechanisms of free fatty acid (FFA) uptake in the vascular endothelium are unclear. In this issue of Cell Metabolism, Ibrahim et al. (2020) discover that FFA uptake is partially mediated by a vectorial, ER-mitochondria link, in which mitochondrial ATP production is locally used for the acyl-CoA synthetase activity of the ER-located fatty acid transport protein 4.iNKT cells are important regulatory cells in metabolic health and disease. In this issue of Cell Metabolism, LaMarche et al. (2020) clarify the origin and heterogeneity of these unconventional T cells and identify the specific signals in adipose tissues that direct their function.The COVID-19 pandemic has driven unprecedented efforts to identify existing treatments that can be quickly and effectively repurposed to reduce morbidity and mortality. In this issue of Cell Metabolism, Zhang et al. (2020) report an association between statin use and improved outcomes in a large observational study of hospitalized COVID-19 patients. Given the widespread availability, low cost, and safety of statins, this promising result should be further investigated in randomized controlled trials.The in vitro cortical slice preparation is a widely used tool for electrophysiological investigation of brain neurophysiology. However, slice quality can be highly variable despite attempts to standardise practice. The purpose of this study was to determine the extent to which this variability is due to sensitivity to aspects of the preparation methodology. The study ultilised the no-magnesium seizure-like event (SLE) model and was in two parts. In the first, slice outcome was quantified following a standardised hypoxic-ischaemic insult applied to pre-prepared slices. The hypoxia-induced changes in SLE activity were used to characterise the effect of tissue damage on commonly measured electrophysiological variables. In the second, multivariate data associated with the slice preparation methodology was collected and related to tissue outcome, according to the same SLE characteristics. Hypoxia-ischaemia damage was reflected most strongly in a reduction in SLE amplitude, inter-event frequency and intra-event high frequency activity. The number of active locations was also markedly reduced. In the second part of the study, between 21% and 47% of outcome variation was attributable to variability in the methodological parameters tested. Most important were slice position from the tissue block, depth of slice submersion during recording and the experience level of the experimenter. The latter showed a paradoxical relationship between inexperience, heightened SLE amplitude and reduced spatial viability. While much of the variation in slice outcome remained unexplained, the factors shown to correlate with tissue viability will aid slice experimentalists in preparing tissue of optimal quality for electrophysiological investigation. In particular, using population event amplitude as the sole criterion of slice quality in the no-magnesium model is overly simplistic and must be viewed in the context of spatial activity.Identification of the brain structures in the magnetic resonance imaging (MRI) of the rat is very important for the experimental work of many neuroscientists. Our intention was to recognize most of the structures without overlapping the MRI sections with the histological templates. Three live rats were used for this study who were examined in a micro-MRI apparatus by performing T2-weighted sequences in serial brain sections. Most of the white matter structures were easily identified, e.g. the anterior commissure, corpus callosum with forceps minor and major, cingulum, external and internal capsules, fornix, stria medullaris and terminalis, cranial nerves, mammillothalamic tract, fasciculus retroflexus, medial and lateral lemniscus, posterior commissure, commissures of the superior and inferior colliculi, medial longitudinal fasciculus, and the cerebral peduncle. Large and small gray matter structures were recognized as well, for example, the anterior olfactory structures, nucleus accumbens, caudate putamen, claustrum, bed nucleus of the stria terminalis, pituitary gland, globus pallidus, amygdala, some midline and intralaminar thalamic nuclei, certain hypothalamic nuclei, hippocampal formation, pineal body, periaqueductal gray matter, lateral and medial geniculate bodies, superior and inferior colliculi, and cranial nerves nuclei. All in all, of the total 160 recognized brain structures, 77 were identified without using the corresponding histological atlases. We believe that our labeled MRI pictures could be an important way for quick orientation for evaluating the effects of the experimental work regarding the rat brain.
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