A5008675529- Regulation of Appetite and Obesity
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Biochemical Analysis and Sensing Techniques
- Sleep and Wakefulness Research
- Hypothalamic control of reproductive hormones
- Parkinson's Disease Mechanisms and Treatments
- Fibroblast Growth Factor Research
- Dietary Effects on Health
- Diet, Metabolism, and Disease
- Parathyroid Disorders and Treatments
- Neurological disorders and treatments
- Neurotransmitter Receptor Influence on Behavior
- Stress Responses and Cortisol
- Adipokines, Inflammation, and Metabolic Diseases
- Circadian rhythm and melatonin
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neuropharmacology Research
- Eating Disorders and Behaviors
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Genetic Syndromes and Imprinting
- Genetics, Aging, and Longevity in Model Organisms
Amsterdam University Medical Centers
2019-2024
University of Amsterdam
2014-2023
Netherlands Institute for Neuroscience
2011-2023
Royal Netherlands Academy of Arts and Sciences
2011-2023
Amsterdam Neuroscience
2019-2021
Amsterdam UMC Location University of Amsterdam
2011-2018
Estrogen plays an important role in the regulation of hypothalamus-pituitary-adrenal (HPA)-axis, but neuroendocrine pathways and estrogen receptor (ER) subtypes involved specific aspects this interaction remain unknown. In a first set experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, by intrahypothalamic microdialysis to ovariectomized rats measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion E2 did not increase...
Rats on different free‐choice (fc) diets for 1 week of either chow, saturated fat and liquid sugar (fc HFHS ), chow HF or HS ) have differential levels neuropeptide Y ( NPY m RNA in the arcuate nucleus. Because these differences were not explained by plasma leptin but did predict subsequent feeding behaviour, present study, we first examined whether sensitivity could explain differences. Second, focused role measured to after 4 weeks choice diets. To determine sensitivity, food intake i.p....
The enzyme type 2 deiodinase (D2) is a major determinant of T₃ production in the central nervous system. It highly expressed tanycytes, specialized cell lining wall third ventricle. During acute inflammation, expression D2 tanycytes up-regulated by mechanism that poorly understood at present, but we hypothesized cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit NFκB) inflammatory signal transduction pathways are involved....
Long-term reduced hypothalamic estrogen signaling leads to increased food intake and decreased locomotor activity energy expenditure, ultimately results in obesity insulin resistance. In the current study, we aimed determine acute obesity-independent effects of on glucose metabolism. We studied endogenous production (EGP) sensitivity during selective modulation systemic or intrahypothalamic estradiol (E2) rats 1 week after ovariectomy (OVX). OVX caused a 17% decrease plasma glucose, which...
During fasting, profound changes in the regulation of hypothalamus-pituitary-thyroid axis occur order to save energy and limit catabolism. In this setting, serum T3 T4 are decreased without an appropriate TSH TRH response reflecting central down-regulation axis. Hepatic thyroid hormone (TH) metabolism is also affected by because type 3 deiodinase (D3) increased, which mediated leptin concentrations. A recent study showed that fasting-induced liver TH sulfotransferases (Sults) uridine...
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and currently under investigation as a treatment eating disorders. DBS this area associated with altered food intake pharmacological OCD risk developing type 2 diabetes. Therefore we examined if NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, period 1 h. To assess effects on blood glucoregulatory hormones,...
Objective Leptin resistance is a common hallmark of obesity. Rats on free-choice high-fat high-sugar (fcHFHS) diet are resistant to peripherally administered leptin. The aim this study was investigate feeding responses central leptin as well the associated changes in mRNA levels hypothalamic and mesolimbic brain areas. Design Methods CHOW or fcHFHS for 8 days received vehicle intracerebro(lateral)ventricularly (ICV) food intake measured 5 h 24 later. Four later, rats were sacrificed after...
The preclinical multicomponent free-choice high-fat high-sucrose (fcHFHS) diet has strong validity to model diet-induced obesity (DIO) and associated maladaptive molecular changes in the central nervous system. fcHFHS-induced obese rats demonstrate increased sensitivity intracerebroventricular infusion of orexigenic Neuropeptide Y (NPY). brain region-specific effects NPY signaling on fcHFHS component selection are not completely understood. For example, fcHFHS-fed have intake chow fat...
The hypothalamic neuropeptide Y (NPY) circuitry is a key regulator of feeding behavior. NPY also acts in the mesolimbic dopaminergic circuitry, where it can increase motivational aspects behavior through effects on dopamine output nucleus accumbens (NAc) and neurotransmission ventral tegmental area (VTA). Endogenous NAc originates from local interneurons afferent projections arcuate (Arc). However, origin endogenous VTA unknown. We determined, normal-weight male Wistar rats, if source local,...
Objective Eating out of phase with the endogenous biological clock alters and metabolic gene expression in rodents can induce obesity type 2 diabetes mellitus. Diet composition also affect expression. This study assessed combined effect diet feeding time on (1) body composition, (2) energy balance, (3) circadian hepatic genes. Methods Male Wistar rats were fed a chow or free‐choice high‐fat, high‐sugar (fcHFHS) diet, either ad libitum food access restricted to light dark period. Body weight,...
Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect day-night feeding rhythm resulting a higher light phase intake. In vitro vivo studies showed that nutrients clock-gene expression. We therefore hypothesized overconsuming sugar alters expression brain structures important for behavior. determined effects free-choice high-fat high-sugar (fcHFHS) diet on rat areas related to reward compared...
Growing evidence demonstrates the role of striatal dopamine system in regulation glucose metabolism. Treatment with antagonists is associated insulin resistance and hyperglycemia, while agonists are used treatment type 2 diabetes. The mechanism underlying effects metabolism, however not fully understood. Here, we provide mechanistic insights into nucleus accumbens shell (sNAc) dopaminergic signaling systemic metabolism.Endogenous production (EGP), blood mRNA expression lateral hypothalamic...
Protein-folding stress at the Endoplasmic Reticulum (ER) occurs in hypothalamus during diet-induced obesity (DIO) and is linked to metabolic disease development. ER buffered by activation of unfolded protein response (UPR), a controlled network pathways inducing set genes that recovers function. However, it unclear whether hypothalamic DIO results from related changes or direct nutrient effects brain. We here investigated mRNA expression UPR markers rats were exposed free choice high-fat...
Objectives: The hypothalamus lies adjacent to the third ventricle and is in close proximity with median eminence (ME), a circumventricular organ an incomplete blood-brain barrier (BBB) which controls direct entry of nutrients into brain. blood-CSF shows dynamic changes upon neuroendocrine events adjusts permeability tight junction (TJ) complex. It has been shown that chronic exposure high-fat diet (HFD) affects BBB permeability. HFD also induces leptin resistance alters neuropeptide...
Abnormal phosphorylation and aggregation of tau is a key hallmark Alzheimer's disease (AD). AD multifactorial neurodegenerative disorder for which Diabetes Mellitus (DM) risk factor. In animal models DM, the induced or exacerbated, however underlying mechanism unknown. addition to metabolic dysfunction, DM characterized by chronic low-grade inflammation. This was reported be associated with neuroinflammatory response in hypothalamus models. Neuroinflammation also implicated development...
We showed previously that rats on a free-choice high-fat, high-sugar (fcHFHS) diet become rapidly obese and develop glucose intolerance within week. Interestingly, neither high-fat (fcHF), although equally hyperphagic, nor (fcHS) consuming more sugar water, intolerance. Here, we investigate whether changes in insulin sensitivity contribute to the observed this is related consumption of saturated fat and/or water. Rats received either fcHFHS, fcHF, fcHS or chow for one performed...
Central dopamine signaling regulates reward-related aspects of feeding behavior, and during diet-induced obesity receptor is altered. Yet, the influence on consumption specific dietary components remains to be elucidated. We have previously shown that 6-hydroxydopamine-mediated lesions neuron terminals in lateral shell nucleus accumbens promotes fat intake rats fed a multi-component free-choice high-fat high-sugar (fcHFHS) diet. It however not yet determined which receptors are responsible...