A5007853808- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Sleep and Wakefulness Research
- Diet and metabolism studies
- Circadian rhythm and melatonin
- Pancreatic function and diabetes
- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Neurobiology and Insect Physiology Research
- Neuropeptides and Animal Physiology
- Birth, Development, and Health
- Receptor Mechanisms and Signaling
- Infant Nutrition and Health
- Diabetes Treatment and Management
- Neurological Disease Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
- Biochemical effects in animals
- Hypothalamic control of reproductive hormones
- Neuroinflammation and Neurodegeneration Mechanisms
- Fibroblast Growth Factor Research
- Nutritional Studies and Diet
- Sulfur Compounds in Biology
- Fatty Acid Research and Health
University of Cambridge
2015-2024
Wellcome/MRC Institute of Metabolic Science
2015-2024
Medical Research Council
2015-2024
Addenbrooke's Hospital
2015-2020
Wellcome Trust
2015-2020
Albert Einstein College of Medicine
2008-2015
Yeshiva University
2015
AgroParisTech
2007
Physiologie de la Nutrition et du Comportement Alimentaire
2004-2006
Institut National de la Recherche Agronomique
2006
In response to nutrient stimuli, the mediobasal hypothalamus (MBH) drives multiple neuroendocrine and behavioral mechanisms regulate energy balance. While central leucine reduces food intake body weight, specific neuroanatomical sites of sensing, downstream neural substrates, neurochemical effectors involved in this regulation remain largely unknown. Here we demonstrate that MBH engages a regulatory circuit by stimulating POMC (proopiomelanocortin) neurons MBH, oxytocin paraventricular...
Tight control of glucose excursions has been a long-standing goal treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated hyperglycemia. Fibroblast growth factor (FGF) 19 is hormone-like enterokine released postprandially that emerged as potential therapeutic agent metabolic disorders, including obesity. Remarkably, FGF19 hypoglycemic actions remain potent models genetic acquired insulin resistance. Here, we provided evidence central...
Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture.Using single cell RNA sequencing, we have generated an atlas gene expression murine POMC neurons.Of 163 neurons, 118 expressed high levels Pomc with little/no Agrp and were considered "canonical" (P+). The other 45/163 low (A+P+). Unbiased clustering analysis P+ revealed four different classes,...
To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons NTS. Ablation NTS Calcr abrogated long-term suppression but not aversive responses, by CALCR agonists. Similarly, activating CalcrNTS decreased intake and body weight (unlike neighboring CckNTS cells) failed to promote aversion, revealing that mediate a non-aversive intake. While both feeding via projections PBN, cells activated CGRPPBN while distinct...
Previous evidence indicates that duodenal lipid sensing engages gut-brain neurocircuits to determine food intake and hepatic glucose production, but a potential role for communication in the control of energy expenditure remains be determined. Here, we tested hypothesis activates gut–brain–brown adipose tissue neuraxis regulate thermogenesis. We demonstrate direct administration lipids into duodenum increases brown fat temperature. Co-infusion local anesthetic tetracaine with abolished...
Bile acids have been implicated as important regulators of glucose metabolism via activation FXR and GPBAR1. We previously shown that FGF19 can modulate handling by suppressing the activity hypothalamic AGRP/NPY neurons. As bile stimulate release FGF19/FGF15 into circulation, we pursued potential to improve tolerance a gut-brain axis involving FGF15/FGF19 within enterocytes FGF receptors on neurons.A 5-day gavage taurocholic acid, mirroring our previous protocol treatment, was performed....
The mediobasal hypothalamus (MBH; arcuate nucleus of the [ARH] and median eminence [ME]) is a key nutrient sensing site for production complex homeostatic feedback responses required maintenance energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation differentiation oligodendrocyte progenitors, leading to new oligodendrocytes in ME specifically. During this nutritional paradigm, perineuronal nets (PNNs), emerging regulators ARH metabolic functions,...
Brown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor raphe pallidus (Rpa).In order selectively manipulate neuron activity, generated transgenic mice expressing channelrhodopsin fused yellow fluorescent protein (YFP) (choline...
The normal function of the mammalian reproductive axis is strongly influenced by physiological, metabolic and environmental factors. Kisspeptin neuropeptides, encoded Kiss1 gene, are potent regulators stimulating gonadodropin releasing hormone secretion from hypothalamus. To understand how modulated higher order neuronal inputs we have mapped afferent circuits into arcuate (ARC) neurons. We used a transgenic mouse that expresses CRE recombinase in neurons for conditional viral tracing with...
This paper provides molecular evidence for a liver glyconeogenic pathway, that is, concomitant activation of hepatic gluconeogenesis and glycogenesis, which could participate in the mechanisms cope with amino acid excess high-protein (HP) fed rats. is based on upregulation phosphoenolpyruvate carboxykinase (PEPCK) gene expression, downregulation glucose 6-phosphatase catalytic subunit (G6PC1) an absence release from isolated hepatocytes restored glycogen stores state HP These effects are...
Nutrient excess in obesity and diabetes is emerging as a common putative cause for multiple deleterious effects across diverse cell types, responsible variety of metabolic dysfunctions. The hypothalamus acknowledged an important regulator whole-body energy homeostasis, through both detection nutrient availability coordination effectors that determine intake utilization, thus preventing cellular excess. However, the mechanisms underlying hypothalamic its impact on peripheral utilization...
Thioredoxin interacting protein (TXNIP) has recently been described as a key regulator of energy metabolism through pleiotropic actions that include nutrient sensing in the mediobasal hypothalamus (MBH). However, role TXNIP neurochemically specific hypothalamic subpopulations and circuits downstream from MBH engaged to regulate homeostasis remain unexplored. To evaluate metabolic activity specifically within arcuate Agrp neurons, we generated Agrp-specific gain-of-function loss-of-function...
Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in availability are detected by the brain adjust iBAT activity maintain homeostasis. Here, we provide evidence that AGRP inhibitory tone represents energy-sparing circuit integrates environmental food cues internal signals of availability. We establish a role for nutrient-sensing mTORC1...
Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration a glucagon-like peptide-1 receptor (GLP-1R) agonist with cholecystokinin receptor-1 (CCKR1) exert synergistic effects on weight loss in obese rodents. Here, we report novel fusion peptide (C2816) comprised stabilized GLP-1R agonist, AC3174, CCKR1-selective AC170222. C2816 was constructed that AC3174 linked to N-terminus AC170222, thus preserving...
The nucleus of the solitary tract (NTS) is emerging as a major site action for appetite-suppressive effects leading pharmacotherapies currently investigated to treat obesity. However, our understanding how NTS neurons regulate appetite remains incomplete. In this study, we used nutrient sensing an entry point characterize stimulus-defined neuronal ensembles engaged by produce physiological satiety. We combined histological analysis, neuroanatomical assessment using inducible viral tracing...
Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity ME mice health or response chronic challenge and determine its relevance regulation energy balance.