A5042273601- Regulation of Appetite and Obesity
- Pancreatic function and diabetes
- Fibroblast Growth Factor Research
- Diet and metabolism studies
- Proteoglycans and glycosaminoglycans research
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Bariatric Surgery and Outcomes
- Sleep and Wakefulness Research
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Neuroscience of respiration and sleep
- Inflammatory Bowel Disease
- Epigenetics and DNA Methylation
- Hypothalamic control of reproductive hormones
- Diabetes and associated disorders
- Eating Disorders and Behaviors
- Apelin-related biomedical research
- Autoimmune and Inflammatory Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- S100 Proteins and Annexins
- Pharmaceutical studies and practices
- Glaucoma and retinal disorders
- 3D Printing in Biomedical Research
Seattle Children's Hospital
2014-2025
University of Washington
2016-2025
Seattle University
2015-2023
Phoenix (United States)
2020
Oregon Health & Science University
2005-2010
Washington Center for Weight Management and Research
2007
Significance Hypoglycemia is an important and frequently encountered complication of diabetes treatment. Here, we identify a subset neurons located in the ventromedial hypothalamic nucleus, activation which both necessary sufficient to mediate adaptive counterregulatory responses hypoglycemia that return low blood glucose levels into normal range. These receive ascending input from lateral parabrachial nucleus turn control via projections anterior bed stria terminalis. Together, this work...
Anorexia and involuntary weight loss are common debilitating complications of a number chronic diseases inflammatory states. Proinflammatory cytokines, including IL-1β, hypothesized to mediate these responses through direct actions on the central nervous system. However, neural circuits which proinflammatory cytokines regulate food intake energy balance remain be characterized. Here we report that IL-1β activates melanocortin system, key neuronal circuit in regulation homeostasis....
Abstract The extracellular matrix (ECM) of the brain comprises unique glycan “sulfation codes” that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate‐glycosaminoglycan (CS‐GAG) containing matrices enmesh neural networks involved in memory and cognition, loss PNN is reported patients with neurocognitive neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC‐MS/MS), we show a clinical diagnosis...
Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications attached CS-GAGs, these matrices play key roles mediating glycan-protein binding, signaling interactions, charged ion buffering underlying circuitry. Histochemical loss PNN has been reported for a range...
Abstract Background Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety tofacitinib UC. Methods is a retrospective review children diagnosed with UC treated from 16 centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary...
Agouti-related protein (AgRP) is an orexigenic neuropeptide produced by neurons in the hypothalamic arcuate nucleus (ARC) that a key component of central neural circuits control food intake and energy expenditure. Disorders homeostasis, characterized hypophagia increased metabolic rate, frequently develop animals with either acute or chronic diseases. Recently, studies have demonstrated proopiomelanocortin-expressing ARC are activated proinflammatory cytokine IL-1β. In current study, we...
Abstract In rodent models of type 2 diabetes (T2D), sustained remission hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as brain area responsible for this effect. To better understand cellular response to FGF1 in MBH, we sequenced >79,000 single-cell transcriptomes from diabetic Lep ob/ob mice obtained on Days 5 after icv either or vehicle. A wide range...
Abstract Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models obesity diabetes. The current work was undertaken to advance our understanding the receptor expression, as sites ligand action by FGF19, FGF21, FGF1 mammalian brain remains unresolved. Recent advances automated RNAscope situ hybridization droplet digital PCR (ddPCR) technology allowed us interrogate central FGFR/beta klotho (Klb)...
To maintain energy homeostasis during cold exposure, the increased demands of thermogenesis must be counterbalanced by intake. investigate neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals placed in a environment and, if so, response is required for associated hyperphagia. We report that AgRP neuron activation occurs rapidly upon acute as do increases both expenditure and intake, suggesting...
Galanin-like peptide (GALP) is a newly discovered hypothalamic neuropeptide, which regulated by leptin and implicated in the regulation of GnRH secretion rodent. We searched human genome database determined that GALP gene comprises six exons, as has been shown for galanin. used rapid amplification cDNA ends to clone full-length (802 bp) macaque homologue found it be highly conserved between at both nucleotide (93%) (94%) levels. Mature predicted 60 amino acids other species, region (9-21)...
The proinflammatory cytokine leukemia inhibitory factor (LIF) is induced in disease states and known to inhibit food intake when administered centrally. However, the neural pathways underlying this effect are not well understood. We demonstrate that LIF acutely inhibits by directly activating pro-opiomelanocortin (POMC) neurons arcuate nucleus of hypothalamus. show POMC express LIF-R, stimulates release anorexigenic peptide, alpha-MSH from ex vivo hypothalami. Transgenic mice lacking gp130,...
Dynamic adjustment of insulin secretion to compensate for changes sensitivity that result from alteration nutritional or metabolic status is a fundamental aspect glucose homeostasis. To investigate the role brain in this coupling process, we used cold exposure as an experimental paradigm because sympathetic nervous system (SNS) helps coordinate major shifts tissue utilization needed ensure increased thermogenic needs are met. We found glucose-induced declined by 50% rats housed at 5°C 28 h,...
We recently reported that in rodent models of type 2 diabetes (T2D), a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1) induces remission hyperglycemia is sustained for weeks. To clarify the peripheral mechanisms underlying this effect, we used Zucker diabetic fatty
To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation blood glucose (BG) level, we combined continuous arterial monitoring with measures of activity a specific subset located hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected conscious, free-living mice during 1-h baseline period subsequent 2-h intervention which BG...
In addition to sustained glucose lowering, centrally administered fibroblast growth factor 1 (FGF1) induces a potent but transient anorexia in animal models of type 2 diabetes. To investigate the mechanism(s) underlying this anorexic response, current work focused on specific neuronal subset located external lateral subdivision parabrachial nucleus marked by expression calcitonin gene-related peptide (elPBNCGRP neurons). These neurons can be activated withdrawal upstream GABAergic inhibitory...
Galanin-like peptide (GALP) is produced in a small population of neurons the arcuate nucleus hypothalamus, and leptin stimulates hypothalamic expression GALP mRNA. Because insulin share common signaling pathways brain, we reasoned that might also be responsive to changes circulating concentrations insulin. To test this hypothesis, first studied effect deficiency on by comparing levels mRNA between normal diabetic animals. Streptozotocin-induced diabetes was associated with significant...
Although the brain is clearly capable of affecting blood glucose levels, whether such effects are important in day-to-day control remains a matter controversy. In this Perspective, we update and expand on previously described brain-centric model homeostasis (1), highlighting recent evidence brain’s capacity to influence biologically defended level circulating part through rapid highly coordinated adjustments both insulin sensitivity secretion. We also discuss possibility that dysfunction...
In rodent models of type 2 diabetes (T2D), sustained remission diabetic hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1). To identify the brain areas responsible for this effect, we first used immunohistochemistry to map hypothalamic distribution phosphorylated extracellular signal–related kinase 1/2 (pERK1/2), marker mitogen-activated protein kinase–ERK signal transduction downstream FGF receptor activation. Twenty minutes...
Galanin-like peptide (GALP) is a hypothalamic neuropeptide that has been implicated in the control of feeding, metabolism, and reproduction. The goal this study was to examine effects central infusions GALP on GnRH LH secretion identify physiological factors influence expression mRNA brain primate species. Infusions into lateral cerebroventricle macaque caused significant increase secretion, which blocked by administration receptor antagonist acyline. However, arcuate nucleus, as determined...