A5032144545- GDF15 and Related Biomarkers
- Nutrition and Health in Aging
- Diabetes Treatment and Management
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Neuropeptides and Animal Physiology
- Pharmacology and Obesity Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Adipose Tissue and Metabolism
- Pain Management and Placebo Effect
- Nausea and vomiting management
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Diabetes Management and Research
- Cancer-related cognitive impairment studies
- Nuclear Receptors and Signaling
- Macrophage Migration Inhibitory Factor
- Dietary Effects on Health
- Pharmacological Effects and Toxicity Studies
- Folate and B Vitamins Research
- Vitamin C and Antioxidants Research
- Biochemical Analysis and Sensing Techniques
- Enhanced Recovery After Surgery
- Sleep and Wakefulness Research
- Hypothalamic control of reproductive hormones
- Plant Disease Resistance and Genetics
University of Pennsylvania
2018-2024
University of Southern California
2024
California University of Pennsylvania
2022
University of Zurich
2011-2017
Swiss Integrative Center for Human Health
2016-2017
Center for Pediatric Endocrinology Zurich
2017
Glucagon-like peptide 1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity diabetes. Patient compliance maximal efficacy of GLP-1 therapeutics are limited by adverse side effects, including nausea emesis. In three different species (i.e., mice, rats, musk shrews), we show that glucose-dependent insulinotropic polypeptide (GIPR) signaling blocks emesis attenuates illness behaviors elicited GLP-1R activation, while maintaining reduced food intake, loss,...
The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there still much to be learned regarding neuronal sites action that underlie its suppressive effects on food intake and body weight. Peripherally administered in rats acts part through central GLP-1Rs both hypothalamus hindbrain. Here, we extend findings supporting a role hindbrain mediating anorectic male rats. To dissociate contribution area postrema (AP) nucleus tractus...
The anorectic and weight-suppressive effects of growth differentiation factor-15 (GDF15) are attracting considerable attention for treating obesity. Current experiments in rats investigate whether GDF15 induces an aversive visceral malaise-based state that mediates its acute effect and, through aversion conditioning, exerts longer-term anorexia. Visceral malaise, conditioned affective food responses (taste reactivity), gastric emptying (GE), intake, body weight evaluated after chronic...
The induction of nausea and emesis is a major barrier to maximizing the weight loss profile obesity medications, therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. development peptide YY (PYY)-based approaches treat are no exception, as PYY receptor agonism often accompanied by vomiting. Here, we sought determine whether glucose-dependent insulinotropic polypeptide (GIP) (GIPR) reduces PYY-induced nausea-like behavior mice. We found central...
To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) semaglutide combined would be a more efficacious antiobesity treatment than either alone by examining neural behavioural mechanisms contributing to their anorectic were common or disparate.Three investigated determine how GDF15 induce anorexia: potentiation intake suppression gastrointestinal satiation signals; reduction in motivation feed; induction visceral malaise. We then...
Nausea and vomiting remain life-threatening obstacles to successful treatment of chronic diseases, despite a cadre available antiemetic medications. Our inability effectively control chemotherapy-induced nausea (CINV) highlights the need anatomically, molecularly, functionally characterize novel neural substrates that block CINV.
Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators tumour‐derived factors are thought to play an important role the aetiology of CACS. However, central peripheral mechanisms contributing CACS insufficiently understood. area postrema (AP) nucleus tractus solitarii two brainstem centres for control eating during acute sickness conditions. Recently, macrophage inhibitory cytokine‐1 (MIC‐1)...
With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools transgenic models for gaining long-term genetic access MOR+ neural types circuits involved in modulating pain, analgesia addiction across species are limited. To address this, we developed catalog MOR promoter (MORp) based constructs packaged into adeno-associated viral...
While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed conjugate of vitamin B12 (B12) bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability retention agonism. Here, we evaluate whether (B12-Ex4) can improve glucose tolerance without producing anorexia malaise.We evaluated effects systemic B12-Ex4...
The gastric hormone ghrelin positively affects energy balance by increasing food intake and reducing expenditure. Ghrelin mimetics are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to characterize the action of nonpeptidergic receptor agonist HM01 on neuronal function, homeostasis muscle mass in healthy rats evaluate its usefulness for CACS rat tumor model. Using extracellular single-unit recordings, we tested whether mimics effects activity arcuate...
Glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat type 2 diabetes mellitus often produce nausea, vomiting, and in some patients, undesired anorexia. Notably, these behavioral effects are caused by direct central GLP-1R activation. Herein, we describe the creation of a agonist conjugate with modified brain penetrance that enhances GLP-1R-mediated glycemic control without inducing vomiting. Covalent attachment exendin-4 (Ex4) dicyanocobinamide (Cbi), corrin ring containing...
Adult neurogenesis in the subgranular zone and subventricular is generally accepted, but its existence other brain areas still controversial. Circumventricular organs, such as area postrema (AP) have recently been described potential neurogenic niches adult brain. The AP major site of action satiating hormone amylin. Amylin has shown to promote formation neuronal projections originating from neonatal rodents role amylin remains unknown. To test this, we first performed an RNA-sequencing rats...
To develop a conjugate of vitamin B12 bound to the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex4) that shows reduced penetrance into central nervous system while maintaining peripheral glucoregulatory function.We evaluated whether Ex4 (B12-Ex4) improves glucose tolerance without inducing anorexia in Goto-Kakizaki (GK) rats, lean type 2 diabetes model an understudied but medically compromised population patients requiring effects GLP-1R agonists anorexia. We also utilized...
The behavioral mechanisms and the neuronal pathways mediated by amylin its long-acting analog sCT (salmon calcitonin) are not fully understood it is unclear to what extent engage overlapping or distinct subpopulations reduce food intake. We here hypothesize that recruit different population mediate their anorectic effects. Viral approaches were used inhibit calcitonin gene-related peptide (CGRP) lateral parabrachial nucleus (LPBN) neurons assess role in amylin's sCT's ability decrease intake...
Growth differentiation factor 15 (GDF15) is a contributor to nausea, emesis, and anorexia following chemotherapy via binding the GFRAL-RET receptor complex expressed in hindbrain neurons. Therefore, GDF15-mediated signaling promising target for improving treatment outcomes patients. We developed peptide-based antagonists of GFRAL that block RET recruitment. Our initial library screen led five novel peptides. Surface plasmon resonance flow cytometric analyses most efficacious this group,...