A5073863454- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroendocrine regulation and behavior
- Fatty Acid Research and Health
- Neuroscience of respiration and sleep
- Lipid metabolism and biosynthesis
- Neurological Disease Mechanisms and Treatments
- Diabetes Treatment and Management
- Sleep and Wakefulness Research
- Receptor Mechanisms and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Cholesterol and Lipid Metabolism
- Cell Image Analysis Techniques
- Diet, Metabolism, and Disease
- PI3K/AKT/mTOR signaling in cancer
- Peroxisome Proliferator-Activated Receptors
- Apelin-related biomedical research
- Drug-Induced Hepatotoxicity and Protection
- 14-3-3 protein interactions
- Birth, Development, and Health
University of Zurich
2016-2025
New York University Press
2024
Cambridge University Press
2024
Université de Bretagne Occidentale
2023
Swiss Integrative Center for Human Health
2017
Czech Academy of Sciences, Institute of Physiology
2016
Rutgers, The State University of New Jersey
2008-2015
Rutgers New Jersey Medical School
2008-2015
East Orange VA Medical Center
2009-2014
We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity a potential means of regulating energy homeostasis. Fura-2 calcium (Ca(2+)) membrane dye imaging, together with pharmacological agents, were used assess oleic acid (OA) alters dissociated VMN from 3- 4-wk-old rats. OA excited up 43% inhibited 29% all independently concentrations. In those 2.5 mM OA, had...
Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess relationship between a high-fat diet (HFD; 60%) intake on feeding serum VMH FA levels, rats were trained to eat low-fat (LFD; 13.5%) or an HFD 3 h/day monitored with microdialysis. Despite having higher had lower but ate less from 6 h refeeding than did LFD rats. However, β-hydroxybutyrate (β-OHB)...
The initial cephalic phase of insulin secretion is mediated through the vagus nerve and not due to glycemic stimulation pancreatic β cells. Recently, IL-1β was shown stimulate postprandial secretion. Here, we describe that this incretin-like effect involves neuronal transmission. Furthermore, found release by originating from microglia. Moreover, activated induce regulated activity hypothalamus in response stimulation. Notably, impaired obesity, both mice humans, mice, dysregulated...
Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) play an integral role in the regulation of glucose, energy homeostasis, development obesity diabetes. Using pharmacologic agents, we previously found that ~50% these responded to oleic acid (OA) by using FA translocator/receptor FAT/CD36 (CD36). For further elucidation CD36 neuronal sensing, ventromedial hypothalamus (VMH) was depleted adeno-associated viral (AAV) vector expressing short hairpin RNA (shRNA) rats....
Amylin acts acutely via the area postrema to reduce food intake and body weight, but it also interacts with leptin over longer periods of time, possibly ventromedial hypothalamus (VMH), increase signaling phosphorylation STAT3. We postulated that amylin enhances VMH by inducing interleukin (IL)-6, which then its gp130 receptor activate STAT3 gene transcription downstream receptor. found components (RAMPs1–3, CTR1a,b) are expressed in cultured astrocytes, neurons, microglia, as well...
Neurotensin (NT) is a peptide expressed in the brain and gastrointestinal tract. Brain NT inhibits food intake, but effects of peripheral are less investigated. In this study, decreased intake both mice rats, which was abolished by antagonist. Using c-Fos immunohistochemistry, we found that activated brainstem hypothalamic regions. The anorexigenic effect preserved vagotomized lasted shorter than sham-operated mice. This combination with strong increase activation area postrema after ip...
Amylin phosphorylates ERK (p-ERK) in the area postrema to reduce eating and synergizes with leptin phosphorylate STAT3 arcuate (ARC) ventromedial (VMN) hypothalamic nuclei food intake body weight. The current studies assessed potential amylin amylin-leptin ARC/VMN interactions on signaling their roles postnatal pathway development. In knockout mice, density of agouti-related protein (AgRP)-immunoreactive (IR) fibers paraventricular nucleus (PVN) was increased, while α-melanocyte-stimulating...
Abstract Defective insulin processing is associated with obesity and diabetes. Prohormone convertase 1/3 (PC1/3) an endopeptidase required for the of neurotransmitters hormones. PC1/3 deficiency genome-wide association studies relate early onset obesity. Here, we find that deletion in obesity-related neuronal cells expressing proopiomelanocortin mildly transiently change body weight fail to produce a phenotype when targeted Agouti-related peptide- or nestin-expressing tissues. In contrast,...
Abstract Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate suppression of food intake and body weight. To understand molecular neural mechanisms cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across rat, mouse, non-human primate...
Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling synergistically reduces food intake body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to hypothalamus (VMH) resistance, impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA...
Obesity has emerged as a major risk factor for insulin resistance leading to the development of type 2 diabetes (T2D). The condition is characterized by high circulating levels adipose-derived hormone leptin and state chronic low-grade inflammation. Pro-inflammatory signaling in hypothalamus associated with decrease central leptin- action impaired systemic glucose tolerance. Intriguingly, not only regulates body weight homeostasis but also acts pro-inflammatory cytokine. Here we demonstrate...
Amylin, a pancreatic hormone and neuropeptide, acts principally in the hindbrain to decrease food intake has recently been shown act as neurotrophic factor control development of area postrema → nucleus solitary tract arcuate hypothalamic paraventricular axonal fiber outgrowth. Amylin is also able activate ERK signaling specifically POMC neurons independently leptin. For investigation physiological role amylin neurons, core component receptor, calcitonin receptor (CTR), was depleted from...
Neurons in the ventromedial and arcuate hypothalamic nuclei (VMN ARC, respectively) mediate many of leptin’s effects on energy homeostasis. Some are also glucosensing, whereby they use glucose as a signaling molecule to regulate their firing rate. We used fura-2 calcium (Ca2+) imaging determine interactions between these two important mediators peripheral metabolism individual VMN neurons mechanisms by which leptin regulates neuronal activity vitro. Leptin excited 24%, inhibited 20%, had...
Maternal obesity accentuates offspring in dams bred to develop diet-induced (DIO) on a 31% fat, high-sucrose, high-energy (HE) diet but has no effect of diet-resistant (DR) dams. Also, only DIO become obese when they and DR are fed HE throughout gestation lactation. We assessed glucose oleic acid (OA) sensitivity dissociated ventromedial hypothalamic nucleus (VMN) neurons from 3- 4-wk old chow or using fura-2 calcium imaging monitor intracellular fluctuations as an index neuronal activity....
Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing shRNA (AAV shRNA) leads to redistribution adipose stores and insulin resistance in outbred rats. This study assessed requirement VMH CD36-mediated for regulation energy glucose homeostasis postnatal day 5 (P5) P21 selectively bred diet-induced obese (DIO) diet-resistant (DR) rats...