Andries Kalsbeek

Academisch Medisch Centrum Universiteit van Amsterdam | AMC · Department of Endocrinology and Metabolism

Aims Alterations in sleep timing can lead to disturbances in glycaemic control, although the evidence is inconsistent. Therefore, this systematic review summarizes results from human intervention studies of altered sleep timing on glycaemic outcomes. Materials and Methods As part of a broader search on the effect of altering timing of sleep, physi...

Microglia play a crucial role in maintaining neuronal health through phagocytosis, a function that becomes compromised during diet-induced obesity and is associated with altered lipid metabolism. Previous research demonstrated that disrupting lipid metabolism in microglia, such as through lipoprotein lipase deficiency, impairs their phagocytic func...

Background: ADHD is highly comorbid with Delayed Sleep Phase Syndrome (DSPS). Both are associated with obesity and diabetes, which can be caused by long-term dysregulations of appetite and glucose metabolism. This study explores hormones involved in these processes and the effects of chronotherapeutic interventions in a small sample of adults with...

Time-restricted eating has shown promise for improving metabolic health in obese humans. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects the microglial brain immune function using Wistar rats. We found that in high-fat diet (HFD)-induced obesity, TRF during the active phase of rats is effective...

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 r...

Background The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterise the 24-h variation in glucose levels in critically ill patients during continuous enteral nutrition after controlling for potential sources of bias. Methods Time-stamped...

The circadian timing system controls glucose metabolism in a time‐of‐day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a per...

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individua...

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signaling, outflow of the autonomic nervous system, and projections to other brain areas. In the past years, single‐cell datasets of the hypothalamus have contributed immensely to the current understandin...

Lipid homeostasis in humans follows a diurnal pattern in muscle and pancreatic islets, altered upon metabolic dysregulation. We employ tandem and liquid-chromatography mass spectrometry to investigate daily regulation of lipid metabolism in subcutaneous white adipose tissue (SAT) and serum of type 2 diabetic (T2D) and non-diabetic (ND) human volunt...

Background The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterize the 24-hour variation in glucose levels in critically ill patients during continuous enteral feeding after controlling for potential sources of bias. Methods Time-stamped...

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signalling, outflow of the autonomic nervous system, and projections to other brain areas. The past years, single-cell datasets of the hypothalamus have contributed immensely to the current understanding...

Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and g...

One possible pathological mechanism underlying hypertension and its related health consequences is dysfunction of the circadian system—a network of coupled circadian clocks that generates and orchestrates rhythms of ≈24 h in behavior and physiology. To better understand the role of circadian function during the development of hypertension, circadia...

A major function of the nervous system is to maintain the constancy of the internal environment. In 1878, Claude Bernard pointed out the remarkable distinction between our highly variable external environment (i.e., the environment that we live in and that is subject to major changes with regard to temperature, humidity, and food availability) and...

Nocturnal light pollution has been rapidly increasing during the last decades and even though dim artificial light at night (ALAN) has been associated with metabolic diseases, its mechanism is still far from clear. Therefore, the aim of our study was to thoroughly analyze the effects of ALAN on energy metabolism, metabolites, metabolic hormones, an...

Eating during the rest phase is associated with metabolic syndrome, proposed to result from a conflict between food consumption and the energy‐saving state imposed by the circadian system. However, in nocturnal rodents, eating during the rest phase (day‐feeding, DF) also implies food intake during light exposure. To investigate whether light exposu...

Aims: Our study addresses underlying mechanisms of disruption of the circadian timing system by low-intensity artificial light at night (ALAN), which is a growing global problem, associated with serious health consequences. Methods: Rats were exposed to low-intensity (~2 lx) ALAN for 2 weeks. Using in situ hybridization, we assessed 24-h profile...

Obesity and type 2 diabetes mellitus (T2DM) are highly prevalent disorders, associated with insulin resistance and chronic inflammation. The brain is key for energy homeostasis and contains many insulin receptors. Microglia, the resident brain immune cells, are known to express insulin receptors (InsR) and to be activated by a hypercaloric environm...

Shift‐workers show an increased incidence of type 2 diabetes mellitus (T2DM). A possible mechanism is the disruption of the circadian timing of glucose homeostasis. Skeletal muscle mitochondrial function is modulated by the molecular clock. We used time‐restricted feeding (TRF) during the inactive phase to investigate how mistimed feeding affects m...

In female mammals, reproductive senescence is a complex process involving progressive ovarian dysfunction, associated with altered central control of the hypothalamic-pituitary-gonadal axis and desynchronization of the circadian system. The objective of this study was to investigate age-dependent changes in the daily regulation of Arg-Phe amide-rel...

Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-...

Objectives: We have previously shown that the combined consumption of fat and a sucrose solution induces overeating, and there is evidence indicating that sucrose drinking directly stimulates fat intake. One neurochemical pathway by which sucrose may enhance fat intake is through the release of endogenous opioids in the nucleus accumbens (NAC). Met...

Opioids are known to affect blood glucose levels, but it remains unclear what exact role they play in the physiological control of glucose metabolism. While there are numerous studies investigating the peripheral effects of opioid stimulation, little is known about how central opioids control blood glucose and which brain areas are involved. One br...

Based on studies describing an increased prevalence of addictive behaviours in several rare sleep disorders and shift workers, a relationship between circadian rhythms and addiction has been hinted for more than a decade. Although circadian rhythm alterations and molecular mechanisms associated with neuropsychiatric conditions are an area of active...

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised.

The circadian system interacts with the mesocorticolimbic reward system to modulate reward and memory in a time-of-day dependent manner. The circadian discrimination of reward, however, remains difficult to address between natural reinforcers and drugs of abuse. Circadian rhythms control cocaine sensitization and conversely cocaine causes long-term...

Central dopamine signaling regulates reward-related aspects of feeding behavior, and during diet-induced obesity dopamine receptor signaling is altered. Yet, the influence of dopamine signaling on the consumption of specific dietary components remains to be elucidated. We have previously shown that 6-hydroxydopamine-mediated lesions of dopamine neu...

Baroreflex sensitivity (BRS) is an important function of the nervous system and essential for maintaining blood pressure levels in the physiological range. In hypertension, BRS is decreased both in man and animals. Although increased sympathetic activity is thought to be the main cause of decreased BRS, hence the development of hypertension, the BR...

Obesity and type 2 diabetes mellitus are major health concerns worldwide. In obese-type 2 diabetic patients, the function of the central brain clock in the hypothalamus, as well as rhythmicity in white adipose tissue (WAT), are reduced. To better understand how peripheral clocks in white adipose tissue (WAT) are synchronized, we assessed the import...

Kisspeptin (Kp) and (Arg)(Phe) related peptide 3 (RFRP-3) are two RF-amides acting in the hypothalamus to control reproduction. In the past 10 years, it has become clear that, apart from their role in reproductive physiology, both neuropeptides are also involved in the control of food intake, as well as glucose and energy metabolism. To investigate...

Female reproductive success relies on proper integration of circadian- and ovarian- signals to the hypothalamic-pituitary-gonadal axis in order to synchronize the preovulatory LH surge at the end of the ovarian follicular stage with the onset of the main active period. In this study, we used a combination of neuroanatomical and electrophysiological...

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the arti...

The prevalence of obesity has increased rapidly in recent years and has put a huge burden on healthcare worldwide. Obesity is associated with an increased risk for many comorbidities, such as cardiovascular diseases, type 2 diabetes and hypertension. The hypothalamus is a key brain region involved in the regulation of food intake and energy expendi...

The circadian system interacts with the mesocorticolimbic reward system to modulate reward and memory in a time-of-day dependent manner. The circadian discrimination of reward however remains difficult to address between natural reinforcers and drugs of abuse. Circadian rhythms control cocaine sensitization and conversely cocaine causes long-term a...

The master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus provides a temporal pattern of sleep and wake that - like many other behavioural and physiological rhythms - is oppositely phased in nocturnal and diurnal animals. The SCN primarily uses environmental light, perceived through the retina, to synchronize its endogenous circadia...

A major function of the nervous system is to maintain a relatively constant internal environment. The distinction between our external environment (i.e., the environment that we live in and that is subject to major changes, such as temperature, humidity, and food availability) and our internal environment (i.e., the environment formed by the fluids...

Neuroendocrine systems together with the autonomic nervous system serve to synchronize physiological processes that keep the body in balance with the environment. Such a process, also called homeostasis, often is thought to keep the conditions in the body constant in a changing environment. The present paper discusses how the brain controls hormone...

Microglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is critical that microglial immune response appropriately adapts to different stressors. The circadian clock controls the cellular process that involves the...

We hypothesize that desynchronization between different metabolically active organs contributes to alterations in glucose homeostasis. In this mini-review we summarize the most recent information on desynchronization between organs due to shift work and shifted food intake patterns and introduce the concept of phenotypic flexibility, a validated t...

Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for b...

Microglia are the immune cells of the brain. Hyperactivation of microglia contributes to the pathology of metabolic and neuroinflammatory diseases. Evidence has emerged that links the circadian clock, cellular metabolism, and immune activity in microglia. Rev-erb nuclear receptors are known for their regulatory role in both the molecular clock and...

Animal studies indicate that hypothalamic dysfunction plays a major role in type 2 diabetes mellitus (T2DM) development, and that insulin resistance and inflammation are important mechanisms involved in this disorder. However, it remains unclear how T2DM and antidiabetic treatments affect the human hypothalamus. Here, we characterized the proopiome...

Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for b...

Lately, the incidence of overweight, obesity, and type 2 diabetes has shown a staggering increase. To prevent and treat these conditions, one must look at their etiology. As life on earth has evolved under the conditions of nature’s 24‐hour light/dark cycle, it seems likely that exposure to artificial light at night (LAN) would affect physiology. I...

Objective Intrinsically photosensitive retinal ganglion cells are most sensitive to short wavelengths and reach brain regions that modulate biological rhythms and energy metabolism. The increased exposure nowadays to artificial light at night (ALAN), especially short wavelengths, perturbs our synchronization with the 24‐hour solar cycle. Here, the...

Objective This study aimed to describe distributions of behavioral circadian disruptors in a free‐living setting among a nonshift working multi‐ethnic population, estimate the associated risk of type 2 diabetes (T2D), and determine whether disruptors account for ethnic differences in T2D. Methods Participants from six ethnic groups were included (...

Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tis...

Objective Epidemiological studies show that shift workers are at increased risk for type 2 diabetes. As modern societies increasingly require shift work, it seems crucial to determine whether there are long‐lasting health effects of rotational shifts. Methods This study examined the after‐effects of 4 weeks of time‐restricted feeding (TRF) during...

Objective Eating out of phase with the endogenous biological clock alters clock and metabolic gene expression in rodents and can induce obesity and type 2 diabetes mellitus. Diet composition can also affect clock gene expression. Here, we assessed the combined effect of diet composition and feeding time on (1) body composition, (2) energy balance,...

In addition to its regulatory role in luteinizing hormone secretion, RFamide related peptide 3 (RFRP3) has also been reported to modulate food intake in several mammalian species. Djungarian hamsters (Phodopus sungorus), like other seasonal mammals, display a remarkable inhibition of RFRP3 expression in winter short day conditions, associated with...

Context The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. Objective To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. Design Observational Setting Amsterdam UMC, location VUMC, and OLVG, Amsterdam Interventions Collect...

In our modern society, the exposure to light at night (LAN) has increased considerably, which may impact human health negatively. Especially exposure to light at night containing short wavelength emissions (~450-500 nm) can disrupt the normal function of the biological clock, altering sleep-wake cycles and inducing metabolic changes. Recently, we r...

Obesity is taking worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar AMP-DNM which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in...

Epidemiological studies indicate that shift-workers have an increased risk of type 2 diabetes mellitus (T2DM). Glucose tolerance and insulin sensitivity both are dependent on the circadian timing system (i.e., the time-of-day) and fasting duration, in rodents as well as humans. Therefore, question is whether manipulation of the circadian timing sys...

Inhibitors of DNA methylation and orexin type-1 receptor antagonists modulate the neurobiological effects driving drugs of abuse and natural reinforcers by activating common brain structures of the mesolimbic reward system. In this study, we applied a self-administration paradigm to assess the involvement of factors regulating DNA methylation proce...

Aims/hypothesis The central pacemaker of the mammalian biological timing system is located within the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. Together with the peripheral clocks, this central brain clock ensures a timely, up-to-date and proper behaviour for an individual throughout the day–night cycle. A mismatch between the cen...

Social jet-lag (SJL) impairs academic performance, specifically for late chronotypes facedwith early start times. Most modern tertiary educational systems have fewer time-tabled contacthours and consequently fewer early starts, which may limit SJL. We performed a pilot study of SJLin a convenience sample of students from Maastricht University, wher...

Background: Disturbance of immunometabolic signaling is a key process involved in the progression of obesity. Microglia-the resident immune cells in the brain, initiate local immune responses. It is known that hypercaloric diets lead to microglial activation. Previously, we observed that hypothalamic microglial cells from mice fed high-fat diet (HF...

Exposure to light at night (LAN) has been associated with serious pathologies, including obesity, diabetes and cancer. Recently we showed that 2 h of LAN impaired glucose tolerance in rats. Several studies have suggested that the autonomic nervous system (ANS) plays an important role in communicating these acute effects of LAN to the periphery. Her...

Human postmortem studies as well as experimental animal studies indicate profound changes in neuropeptide expression in the suprachiasmatic nucleus (SCN) in several pathological conditions including hypertension. In addition, animal experimental observations show that the SCN peptides, vasopressin (AVP) and vasoactive intestinal peptide (VIP) are e...

Aims/hypothesis Animal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with...

Many animals exhibit remarkable metabolic and reproductive adaptations to seasonal changes in their environment. When day length shortens, Djungarian hamsters (Phodopus sungorus) reduce their body weight and inhibit their reproductive activity, whereas the opposite occurs in springtime. These physiological adaptations are considered to depend on ph...