A5036013287- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Hypothalamic control of reproductive hormones
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Birth, Development, and Health
- Animal Genetics and Reproduction
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Reproductive Biology and Fertility
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Plant Reproductive Biology
- Child Nutrition and Water Access
- Sleep and Wakefulness Research
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Ovarian function and disorders
- Nutrition, Genetics, and Disease
- Connexins and lens biology
- Animal Nutrition and Physiology
- Obesity and Health Practices
- Reproductive System and Pregnancy
- RNA regulation and disease
University of Arkansas for Medical Sciences
2016-2025
Arkansas Department of Agriculture
2024
Instituto de Neurociencias
2023
The peripheral nervous system harbors a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on Schwann cells that orchestrate breakdown resynthesis of myelin and, at the same time, support axonal regrowth. How meet high metabolic demand required for repair remains poorly understood. We here report injury induces adipocyte glial signaling identify adipokine leptin as an upstream regulator adaptation in regeneration....
The adipokine leptin signals the body's nutritional status to brain and particularly, hypothalamus. However, receptors can be found all throughout body, including pituitary. It is known that permissive for reproduction, mice cannot produce (Lep/Lep) are infertile. Many studies have pinpointed leptin's regulation of reproduction exist at levels hypothalamic-pituitary-gonadal axis. We previously shown deleting signaling portion receptor specifically in gonadotropes impairs fertility female...
Abstract Anterior pituitary somatotropes respond to metabolic signals from the adipokine leptin optimize functional responses body’s nutritional state via growth hormone (GH) secretion. Molecular targets of in include GH, GH-releasing receptor (GHRHR), and, females, transcription factor POU1F1, all which are dependent on stimulation for expression. To identify trophic mechanisms underlying action upon somatotropes, we analyzed single-cell gene transcriptomes comparing pituitaries a female...
Leptin, the product of Lep gene, reports levels adiposity to hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers function, suggesting that leptin may be important their maintenance. This hypothesis was tested new animal model exon 17 receptor (Lepr) protein selectively deleted somatotropes by Cre-loxP technology. Organ genotyping confirmed recombination floxed LepR allele only...
The adipokine, leptin (LEP), is a hormonal gateway, signaling energy stores to appetite-regulatory neurons, permitting reproduction when are sufficient. Dual-labeling for LEP receptors (LEPRs) and gonadotropins or GH revealed 2-fold increase in LEPR during proestrus, some of which was seen LH gonadotropes. We therefore investigated functions gonadotropes with Cre-LoxP technology, deleting the domain (Lepr-exon 17) Cre-recombinase driven by rat LH-β promoter (Lhβ-cre). Selectivity deletion...
Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and pituitary gland among other tissues. Best known for its role in regulating appetite energy expenditure, leptin largely proportion to cells. also important maintenance function of GH cells pituitary. This was shown when deletion receptors on somatotropes caused decreased numbers circulating GH, adult-onset obesity. To determine source most vital cell types, we compared two different knockout models with...
We recorded the effects of administration stimulant Modafinil on amplitude sleep state-dependent auditory P13 evoked potential in freely moving rats, a measure arousal thought to be generated by cholinergic arm reticular activating system, specifically pedunculopontine nucleus (PPN). Groups rats were implanted for recording responses and intracranial injections into PPN neuroactive agents determined. The showed that increased dose-dependent manner at doses 100, 200, 300 µM. effect was...
Alzheimer's disease (AD) is associated with disturbances in blood glucose regulation, and type-2 diabetes elevates the risk for dementia. A role amyloid-β peptide (Aβ) linking these age-related conditions has been proposed, tested primarily transgenic mouse lines that overexpress mutated amyloid precursor protein (APP). Because APP its own impacts on we examined BRI-Aβ42 line ("Aβ42-tg"), which produces extracellular Aβ1-42 CNS without elevation of APP. We also looked interactions...
Leptin receptor (LEPR) signaling controls appetite and energy expenditure. Somatotrope-specific deletion of the LEPRb isoform causes GH deficiency obesity. The present study selectively ablated Lepr exon 1 in somatotropes, which removes signal peptide, causing loss all isoforms LEPR. Excision was restricted to pituitary, mutant somatotropes failed respond leptin. Young (2–3 mo) males showed a severe 84% reduction serum levels more than 60% immunolabeled cells compared with 41%–42% reductions...
Abstract The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of wide variety physiological processes including reproduction, growth, metabolism and stress responses. distinct hormone-producing cell lineages within the display remarkable levels plasticity allow remodeling relative proportions each population to meet organismal demands. molecular mechanisms governing have not been fully elucidated. Our recent studies implicated role Musashi family...
The cyclic expression of pituitary gonadotropin-releasing hormone receptors (GnRHRs) may be an important checkpoint for leptin regulatory signals. Gonadotrope Lepr-null mice have reduced GnRHR levels, suggesting these targets. To determine if stimulated directly, primary cultures or pieces were exposed to 1 100 nM leptin. Leptin increased protein levels and the percentages gonadotropes that bound biotinylated analogs (bio-GnRH) but had no effect on Gnrhr messenger RNA (mRNA). An in silico...
Pituitary somatotropes perform the key function of coordinating organismic growth and body composition with metabolic signals. However, mechanism by which they sense respond to signals via adipokine leptin is unknown. The complex interplay between heterogeneous cell types pituitary confounds identification somatotrope-specific mechanisms. Somatotropes represent 30%–40% anterior population are derived from a lineage cells that activated Pit-Oct-Unc domain family class 1 transcription factor...
Mice with somatotrope-specific deletion of the Janus kinase binding site in leptin receptors are GH deficient as young adults and become obese by 6 months age. This study focused on metabolic status (3-4.5 month old) preobese mutant mice. These mutants had normal body weights, lean mass, serum leptin, glucose, triglycerides. Mutant males females showed significantly higher respiratory quotients (RQ) lower energy output, resulting from a volume CO(2) output O(2) consumption. Deletion were...
Deletion of the signaling domain leptin receptors selectively in somatotropes, with Cre-loxP technology, reduced percentage immunolabeled GH cells and serum GH. We hypothesized that deficit occurred when leptin's postnatal surge failed to stimulate an expansion cell population. To learn more about deficiency cells, we tested their expression GHRH mRNA restorative potential secretagogue stimulation vitro. In freshly plated dissociated pituitary from control male mice, alone (0.3 nM) increased...
Abstract In normal individuals, pituitary somatotrophs optimise body composition by responding to metabolic signals from leptin. To identify mechanisms behind the regulation of leptin, we used Cre‐LoxP technology delete leptin receptors (LEPR) selectively in and developed populations purified fluorescence‐activated cell sorting (FACS) that contained 99% somatotrophs. FACS‐purified, Lepr ‐null showed reduced levels growth hormone (GH), hormone‐releasing receptor (GHRHR), Pou1f1 proteins Gh (...
The adipokine leptin regulates energy homeostasis through ubiquitously expressed receptors. Leptin has a number of major signaling targets in the brain, including cells anterior pituitary (AP). We have previously reported that mice lacking receptors AP somatotropes display growth hormone (GH) deficiency, metabolic dysfunction, and adult-onset obesity. Among other targets, promotes increased levels transcription factor POU1F1, which turn specification somatotrope, lactotrope, thyrotrope cell...
Abstract Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production functional endoplasmic reticula. Obesity adds stress to tissues, requiring them adapt inflammation oxidative stress, adding their allostatic load. We hypothesized that is vulnerable the obesity. Here, we utilized 10- 15-week high-fat diet (HFD, 60%) in thermoneutral environment promote obesity, testing both male female...
The anterior pituitary controls key biological processes, including growth, metabolism, reproduction, and stress responses through distinct cell types that each secrete specific hormones. cells show a remarkable level of type plasticity mediates the shifts in hormone-producing populations are required to meet organismal needs. molecular mechanisms underlying not well understood. Recent work has implicated stem specifically, mRNA binding proteins Musashi family control identity. In this study...
Abstract Most psychiatric and neurological disorders exhibit sleep disorders, in some cases presage the disease. Study of control waking has potential for making a major impact on number translational neuroscience research this area critical. One element reticular activating system (RAS) is pedunculopontine nucleus (PPN), which cholinergic arm RAS, projects to thalamus trigger thalamocortical rhythms brainstem modulate muscle tone locomotion. We developed program using slices containing PPN...
Abstract Leptin regulates food intake and energy expenditure (EE) is produced in adipocytes, the pituitary, several other tissues. Animals that are leptin or receptor deficient have major metabolic complications, including obesity. This study tests hypothesis pituitary somatotrope may contribute a source of maintains some these functions. We created 2 different tissue-specific knockout animals: Somatotrope-Lep-null model an Adipocyte-Lep-null model. Metabolic analysis both models, along with...
The developing pituitary is a rapidly changing environment that constantly meeting the physiological demands of growing organism. During early postnatal development, anterior refining patterns hormone secretion in response to numerous genetic factors. Our laboratory previously developed somatotrope leptin receptor (LEPR) deletion mouse model had decreased lean body mass, disrupted metabolism, GH stores and was deficient as an adult. To understand how LEPR somatotropes altered GH, we turned...