A5044637085- Regulation of Appetite and Obesity
- Neuroscience of respiration and sleep
- Sleep and Wakefulness Research
- Neuropeptides and Animal Physiology
- Circadian rhythm and melatonin
- Receptor Mechanisms and Signaling
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Ion Channels and Receptors
- Genetics and Neurodevelopmental Disorders
- Eating Disorders and Behaviors
- Erythrocyte Function and Pathophysiology
- Biochemical Analysis and Sensing Techniques
- Pharmacological Effects and Assays
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes Treatment and Management
- Pharmacology and Obesity Treatment
- Dietary Effects on Health
- Heart Rate Variability and Autonomic Control
- Genetic Syndromes and Imprinting
University of Manchester
2013-2022
LMC Diabetes & Endocrinology (Canada)
2013-2016
University of Liverpool
2011-2015
Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase expenditure. Some the cellular pathways mediating leptin's anorectic actions are identified, but those thermogenic effects have proven more difficult decipher. We define population neurons in dorsomedial hypothalamic nucleus (DMH) containing RFamide PrRP, activated by leptin. Disruption Lepr selectively these cells blocks responses leptin causes obesity. A separate...
The paraventricular nucleus (PVN) of the hypothalamus has been described as "autonomic master controller". It co-ordinates critical physiological responses through control hypothalamic-pituitary-adrenal (HPA)-axis, and by modulation sympathetic parasympathetic branches central nervous system. PVN comprises several anatomical subdivisions, including parvocellular/ mediocellular subdivision, which contains neurones projecting to medulla spinal cord. Consensus indicates that output from...
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications to reduce appetite and body weight. These actions centrally mediated; however, the neuronal substrates involved poorly understood.We employed a combination of neuroanatomical, genetic, behavioral approaches in mouse investigate involvement caudal brainstem cholecystokinin-expressing neurons effect GLP-1RA exendin-4. We further confirmed key neuroanatomical findings non-human primate brain.We found that required...
Transient receptor potential vanilloid type 4 (TRPV4) and calcium-activated potassium channels (KCa ) mediate osmosensing in many tissues. Both TRPV4 KCa are found the paraventricular nucleus (PVN) of hypothalamus, an area critical for sympathetic control cardiovascular renal function. Here, we have investigated whether functionally couple to PVN parvocellular neurones characterized, pharmacologically, subtype channel involved.
Background: Glucose-sensing neurons are located in several parts of the brain, but concentrated ventromedial nucleus hypothalamus (VMH). The importance these VMH glucose homeostasis is well established, however, little known about their individual identity. In present study, we identified a distinct glucose-sensing population and explored its place glucose-regulatory network. Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, ability pituitary adenylate cyclase-activating...
Abstract To study the effects of an analog gut-produced hormone peptide YY (PYY3-36), which has increased selectivity for Y2 receptor; specifically, to record its on food intake and hypothalamic neuropeptide Y/agouti-related (NPY/AgRP) neuron activity. NNC0165-1273, a modified form PYY3-36 with potent at receptor (>5000-fold over Y1, 1250-fold Y4, 650-fold Y5 receptor), was tested in vivo vitro mouse models. NNC0165-1273 fivefold lower relative affinity compared PYY3-36, but >250-,...
The alternatively spliced trimeric G-protein subunit XLαs, which is involved in cAMP signalling, encoded by the Gnasxl transcript of imprinted Gnas locus. XLαs deficient mice show neonatal feeding problems, leanness, inertia and a high mortality rate. Mutants that survive to weaning age develop into healthy fertile adults, remain lean despite elevated food intake. adult metabolic phenotype can be attributed increased energy expenditure, appears caused sympathetic nervous system activity. To...
New Findings What is the central question of this study? Previously, we showed that Gnasxl knock‐out mice are lean and hypermetabolic, with increased sympathetic stimulation adipose tissue. Do these also display elevated cardiovascular tone? Is brain glucagon‐like peptide‐1 system involved? main finding its importance? knock‐outs have blood pressure, heart rate body temperature. Heart variability analysis suggests an tone. The sympatholytic reserpine had stronger effects on in compared...
Several reports have shown that the periventricular region of brain, including paraventricular nucleus (PVN), is critical to sensing and responding changes in plasma osmolality. Further studies also implicate transient receptor potential ion channel, type V4 (TRPV4) channel this homeostatic behaviour. In previous work we TRPV4 channels couple calcium-activated potassium PVN decrease action firing frequency response hypotonicity. present study investigated whether, similarly,...
Here we show that central administration of pyroglutamylated arginine-phenylamine-amide peptide (QRFP/26RFa) increases both food intake and locomotor activity, without any significant effect on energy expenditure, thermogenesis or reward. Germline knock out either the mouse QRFP receptor orthologs, Gpr103a Gpr103b , did not produce a metabolic phenotype. However, receptors are required for centrally administered to increase feeding activity. As injection activated orexin/hypocretin neurons...