Doublecortin-like knockdown in mice attenuates obesity by stimulating energy expenditure in adipose tissue.

Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism.

The role of the circadian system in the etiology of depression.

Circadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily functions including appetite, sleep, activity and cortisol levels. The circadian clock synchronizes itself to the external world mainly by environmental light cues and can be disturbed by a variety of factors, including shift-work, jet-lag, stress, ageing and artificial light at night.

Impact of a dTcaP booster vaccine awareness campaign initiated by the French national health insurance for adults aged 25 years in 2021.

Background: Vaccination schedules differ from country to country. In France, the diphtheria, tetanus, pertussis, poliomyelitis (dTcaP) booster vaccine coverage for adults aged 25 has been lower than those recommended. We evaluated the impact of an awareness campaign undertaken by the French national health insurance system in 2021.

αβ-T Cells Engineered to Express γδ-T Cell Receptors Can Kill Neuroblastoma Organoids Independent of MHC-I Expression.

Currently ~50% of patients with a diagnosis of high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression of neuroblastoma represents a major challenge for T cell-mediated immunotherapy. Here, we propose a novel T cell-based immunotherapy approach for neuroblastoma, based on the use of TEG002, αβ-T cells engineered to express a defined γδ-T cell receptor, which can recognize and kill target cells independent of MHC-I.

Doublecortin-like expressing astrocytes of the suprachiasmatic nucleus are implicated in the biosynthesis of vasopressin and influences circadian rhythms.

We have recently identified a novel plasticity protein, doublecortin-like (DCL), that is specifically expressed in the shell of the mouse suprachiasmatic nucleus (SCN). DCL is implicated in neuroplastic events, such as neurogenesis, that require structural rearrangements of the microtubule cytoskeleton, enabling dynamic movements of cell bodies and dendrites. We have inspected DCL expression in the SCN by confocal microscopy and found that DCL is expressed in GABA transporter-3 (GAT3)-positive astrocytes that envelope arginine vasopressin (AVP)-expressing cells.

Group housing and social dominance hierarchy affect circadian activity patterns in mice.

In this study, we investigated the effect of social environment on circadian patterns in activity by group housing either six male or six female mice together in a cage, under regular light-dark cycles. Based on the interactions among the animals, the social dominance rank of individual mice was quantitatively established by calculating Elo ratings. Our results indicated that, during our experiment, the social dominance hierarchy was rapidly established, stable yet complex, often showing more than one dominant mouse and several subordinate mice.

Continuous Light Does Not Affect Atherosclerosis in APOE*3-Leiden.CETP Mice.

Artificial light exposure is associated with dyslipidemia in humans, which is a major risk factor for the development of atherosclerotic cardiovascular disease. However, it remains unclear whether artificial light at night can exacerbate atherosclerosis. In this study, we exposed female APOE*3-Leiden.

Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, and Nasu Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy are both underrecognized progressive degenerative white matter diseases that can present with young dementia, leukoencephalopathy and brain calcifications. We report and compare three cases in terms of clinical phenotype, imaging and neuropathological findings. Both cases have led to the identification of two novel causal mutations.

A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening.

Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism.

Environmental 24-hr Cycles Are Essential for Health.

Circadian rhythms are deeply rooted in the biology of virtually all organisms. The pervasive use of artificial lighting in modern society disrupts circadian rhythms and can be detrimental to our health. To investigate the relationship between disrupting circadian rhythmicity and disease, we exposed mice to continuous light (LL) for 24 weeks and measured several major health parameters.

USF1 deficiency activates brown adipose tissue and improves cardiometabolic health.

USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis.

Neural activity in the suprachiasmatic circadian clock of nocturnal mice anticipating a daytime meal.

Circadian rhythms in mammals are regulated by a system of circadian oscillators that includes a light-entrainable pacemaker in the suprachiasmatic nucleus (SCN) and food-entrainable oscillators (FEOs) elsewhere in the brain and body. In nocturnal rodents, the SCN promotes sleep in the day and wake at night, while FEOs promote an active state in anticipation of a predictable daily meal. For nocturnal animals to anticipate a daytime meal, wake-promoting signals from FEOs must compete with sleep-promoting signals from the SCN pacemaker.

Plasticity of circadian clocks and consequences for metabolism.

The increased prevalence of metabolic disorders and obesity in modern society, together with the widespread use of artificial light at night, have led researchers to investigate whether altered patterns of light exposure contribute to metabolic disorders. This article discusses the experimental evidence that perturbed environmental cycles induce rhythm disorders in the circadian system, thus leading to metabolic disorders. This notion is generally supported by animal studies.

Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity.

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure.

Lack of exercise leads to significant and reversible loss of scale invariance in both aged and young mice.

In healthy humans and other animals, behavioral activity exhibits scale invariance over multiple timescales from minutes to 24 h, whereas in aging or diseased conditions, scale invariance is usually reduced significantly. Accordingly, scale invariance can be a potential marker for health. Given compelling indications that exercise is beneficial for mental and physical health, we tested to what extent a lack of exercise affects scale invariance in young and aged animals.

The suprachiasmatic nuclei as a seasonal clock.

In mammals, the suprachiasmatic nucleus (SCN) contains a central clock that synchronizes daily (i.e., 24-h) rhythms in physiology and behavior.

Regulation of circadian and acute activity levels by the murine suprachiasmatic nuclei.

The suprachiasmatic nuclei (SCN) coordinate the daily sleep-wake cycle by generating a circadian rhythm in electrical impulse frequency. While period and phase of the SCN rhythm have been considered as major output parameters, we propose that the waveform of the rhythm of the SCN also has significance. Using implanted micro-electrodes, we recorded SCN impulse frequency in freely moving mice and manipulated its circadian waveform by exposing mice to light-dark (LD) cycle durations ranging from 22 hours (LD 11:11) to 26 hours (LD 13:13).

The brain modulates insulin sensitivity in multiple tissues.

Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system.

Glucocorticoid excess induces long-lasting changes in body composition in male C57Bl/6J mice only with high-fat diet.

Glucocorticoid (GC) overexposure period as observed in Cushing's syndrome (CS) is associated with the metabolic syndrome and cardiovascular disease, which persist after long-term correction of GC excess. We performed a mouse study to identify factors that modulate metabolic recovery from a GC overexposure period. Male C57Bl/6J mice, fed a low-fat diet (LFD) or a high-fat diet (HFD), received corticosterone (CORT) (50 μg/mL) or vehicle in the drinking water for 4 weeks, followed by an 8-week washout period.

[Illness, health and sunlight].

New scientific insights show that the influence of sunlight on health is profound. Recent data suggest that our skin is well adapted to the Dutch climate, but changes in the exposure pattern cause a steady increase in skin cancer. These changes mainly consist of a decrease in daily exposure and a shift from a regular to an intermittent exposure.

The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

Background And Purpose: Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro.

Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity.

Circadian rhythm disturbances are observed in, e.g., aging and neurodegenerative diseases and are associated with an increased incidence of obesity and diabetes.

The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity.

Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass.

Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.

The biogenesis of exosomes, small secreted vesicles involved in signalling processes, remains incompletely understood. Here, we report evidence that the syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin control the formation of exosomes. Syntenin interacts directly with ALIX through LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal budding of endosomal membranes.

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.

Objective: Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake.