A5010846794- Regulation of Appetite and Obesity
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Neuroendocrine regulation and behavior
- Sleep and Wakefulness Research
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes Treatment and Management
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Biomedical Research and Pathophysiology
- Pharmacology and Obesity Treatment
- Diet and metabolism studies
- Advanced Fluorescence Microscopy Techniques
- Neuroscience of respiration and sleep
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Stress Responses and Cortisol
- Fatty Acid Research and Health
- Olfactory and Sensory Function Studies
- Adipose Tissue and Metabolism
Centre National de la Recherche Scientifique
2020-2023
Université Paris Cité
2020-2023
Unit of Functional and Adaptive Biology
2020-2023
University of Minnesota
2023
Amsterdam University Medical Centers
2019
University of Amsterdam
2016-2019
Amsterdam UMC Location University of Amsterdam
2012-2017
Universidad Nacional Autónoma de México
2016
Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) bitter GPCTRs (T2R116, T2R118, T2R138 T2R104), as well α-subunits associated signalling complex (αGustducin, Gα14 αTransducin), in oral extra-oral tissues from lean obese mice, remains poorly characterized. We focused on impact obesity brain areas involved energy homeostasis, namely hypothalamus brainstem....
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations the gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism GlcCer may therefore play a role neuropathology. Besides lysosomal GBA, cells contain non-lysosomal glucosylceramidase (GBA2). Given that two β-glucosidases...
Abstract Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of hypothalamus (PVN), mainly via sympathetic autonomic nervous system (ANS) directly stimulating Cort release from adrenal gland and corticotropin-releasing hormone targeting adenohypophysis to adrenocorticotropic (ACTH). feeds back through glucocorticoid receptors (GRs). Here we show male Wistar rats that PVN neurons projecting do not express GRs, leaving question how ANS gets information...
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity glucocerebrosidase (GBA). In cells, also degraded outside lysosomes the enzyme glucosylceramidase 2 (GBA2) which inherited deficiency associated with ataxias. The interest in GBA and metabolism brain has grown following notion that mutations gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed β-glucopyranosyl-configured cyclophellitol-epoxide...
Astrocytes are a major type of glial cell in the mammalian brain, essentially regulating neuronal development and function. Quantitative imaging represents an important approach to study astrocytic signaling neural circuits. Focusing on Ca2+ activity, key pathway implicated astrocye-neuron interaction, we here report strategy combining fast light sheet fluorescence microscopy (LSFM) correlative screening-based time series analysis, map activity domains astrocytes living nerve tissue. Light...
Galactosylceramidase (GALC) is the lysosomal β-galactosidase responsible for hydrolysis of galactosylceramide. Inherited deficiency in GALC causes Krabbe disease, a devastating neurological disorder characterized by accumulation galactosylceramide and its deacylated counterpart, toxic sphingoid base galactosylsphingosine (psychosine). We report design application fluorescently tagged activity-based probe (ABP) sensitive specific labeling active molecules from various species. The consists...
The suprachiasmatic nucleus (SCN) and arcuate (ARC) have reciprocal connections; catabolic metabolic information activates the ARC inhibits SCN neuronal activity. Little is known about influence of on ARC. Here, we investigated whether modulated sensitivity to conditions. activity, as determined by c-Fos immunoreactivity, was increased after a hypoglycemic stimulus 2-deoxyglucose (2DG). highest activity 2DG found at end light period (zeitgeber 11, ZT11) with lower in beginning 2, ZT2),...
Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in lysosomes visceral macrophages. Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration recombinant GBA containing mannose-terminated N-linked glycans, mediating selective uptake by macrophages expressing mannose-binding lectin(s). Two preparations distinct glycans are registered Europe...
Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents. Moreover, demonstrate mechanism mediating these favorable actions depends oral,...
ABSTRACT Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior both dramatically altered obesity, a multifactorial disease resulting from genetic environmental factors. In mice human, exposure to calorie-dense food has been associated with increased astrocyte reactivity pro-inflammatory response the brain. Although our understanding how astrocytes regulate brain recently flourish, whether striatal contribute regulating...
ABSTRACT The control of body weight and glucose homeostasis are the bedrock type 2 diabetes medication. Therapies based on co-administration glucagon-like peptide-1 (GLP-1) long-acting analogues insulin becoming popular in treatment T2D. Both GLP-1 receptors (InsR GLP1-R, respectively) expressed brain regions critically involved regulation energy homeostasis, suggesting a possible cooperative action. However, mechanisms underlying synergistic action GLP-1R agonists loss remain largely...
Abstract Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior both dramatically altered obesity, a multifactorial disease resulting from genetic environmental factors. In mice humans, exposure to calorie-dense food has been associated with increased astrocytes reactivity pro-inflammatory response the brain. Although our understanding how regulate brain recently flourish, whether striatal contribute regulating food-related...
The hypothalamus is key in the control of energy balance, but strategies targeting hypothalamic neurons have failed to provide viable options treat most metabolic diseases. Conversely, role astrocytes systemic has remained largely unexplored. Here, we show that obesity promotes anatomically restricted exacerbated Ca 2+ activity paraventricular nucleus (PVN) astrocytes. Bidirectional chemogenetic manipulation astrocyte lean mice stimulated or inhibited neighboring parvocellular neurons....
Summary The hypothalamus is key in the control of energy balance. However, to this day strategies targeting hypothalamic neurons failed provide viable option treat most metabolic diseases. Conversely, role astrocytes systemic has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling astrocyte activity. In paraventricular nucleus (PVN) hypothalamus, chemogenetic manipulation results bidirectional neighboring neuron activity, autonomic outflow,...
The hypothalamus is key in the control of energy balance. However, to this day strategies targeting hypothalamic neurons failed provide viable option treat most metabolic diseases. Conversely, role astrocytes systemic has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling astrocyte activity. In paraventricular nucleus (PVN) hypothalamus, chemogenetic manipulation results bidirectional neighboring neuron activity, autonomic outflow, glucose...