Sweet taste of heavy water.

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish DO from HO by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners.

GPR10 gene deletion in mice increases basal neuronal activity, disturbs insulin sensitivity and alters lipid homeostasis.

G-protein-coupled receptor GPR10 is expressed in brain areas regulating energy metabolism. In this study, the effects of GPR10 gene deficiency on energy homeostasis in mice of both sexes fed either standard chow or a high-fat diet (HFD) were studied, with a focus on neuronal activation of PrRP neurons, and adipose tissue and liver metabolism. GPR10 deficiency in males upregulated the phasic and tonic activity of PrRP neurons in the nucleus of the solitary tract.

Iodination of CART(61-102) peptide: Preserved binding and anorexigenic activity in mice.

CART (cocaine- and amphetamine-regulated transcript) peptides are involved in food intake regulation, stress, and other physiological functions. Although CART peptides have been known for over 25 years, their receptor(s) have not yet been characterized. In this short review, we will summarize our previous studies, where we reported specific binding of I-CART(61-102) to PC12 rat pheochromocytoma cells.

Mass spectrometry imaging of free-floating brain sections detects pathological lipid distribution in a mouse model of Alzheimer's-like pathology.

Mass spectrometry imaging (MSI) is a modern analytical technique capable of monitoring the spatial distribution of compounds within target tissues. Collection and storage are important steps in sample preparation. The recommended and most widely used preservation procedure for MSI is freezing samples in isopentane and storing them at temperatures below -80 °C.

Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice.

Lack of leptin production in ob/ob mice results in obesity and prediabetes that could be partly reversed by leptin supplementation. In the hypothalamus, leptin supports the production of prolactin-releasing peptide (PrRP), an anorexigenic neuropeptide synthesized and active in the brain. In our recent studies, the palmitoylated PrRP analog palm11-PrRP31 showed a central anorexigenic effect after peripheral administration.

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties.

Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10.

The use of 1,5-diaminonaphthalene for matrix-assisted laser desorption/ionization mass spectrometry imaging of brain in neurodegenerative disorders.

The selection of a suitable matrix and deposition technique constitutes a critical step in successful matrix-assisted laser desorption/ionization mass spectrometry imaging measurement. In the present work, we compared three techniques of matrix deposition, specifically, sublimation and spraying of 1,5-diaminonaphthalene with two automatic sprayers, ImagePrep and iMatrixSpray. The studied methods were evaluated in experiments for the analysis of lipid composition in the brains of two mouse models of neurodegeneration: APP/PS1 mice with plaques of amyloid β (Aβ) peptides and THY-Tau22 mice with pathologically hyperphosphorylated Tau protein, two hallmarks of Alzheimer's disease-like pathology.

Lipidized Prolactin-Releasing Peptide Agonist Attenuates Hypothermia-Induced Tau Hyperphosphorylation in Neurons.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of extracellular amyloid plaques and intraneuronal neurofibrillary tangles. These tangles mainly consist of hyperphosphorylated tau protein. As it induces tau hyperphosphorylation in vitro and in vivo, hypothermia is a useful tool for screening potential neuroprotective compounds that ameliorate tau pathology.

Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology.

Obesity and type 2 diabetes mellitus (T2DM) are important risk factors for Alzheimer's disease (AD). Drugs originally developed for T2DM treatment, e.g.

Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy.

Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology.

Lipidized prolactin-releasing peptide improved glucose tolerance in metabolic syndrome: Koletsky and spontaneously hypertensive rat study.

Background/objectives: Prolactin-releasing peptide (PrRP) has a potential to decrease food intake and ameliorate obesity, but is ineffective after peripheral administration. We have previously shown that our novel lipidized analogs PrRP enhances its stability in the circulation and enables its central effect after peripheral application. The purpose of this study was to explore if sub-chronic administration of novel PrRP analog palmitoylated in position 11 (palm-PrRP31) to Koletsky-spontaneously hypertensive obese rats (SHROB) could lower body weight and glucose intolerance as well as other metabolic parameters.

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity.

Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability.

Prolactin-releasing peptide: a new tool for obesity treatment.

Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood-brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP).

Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats.

Obesity is an escalating epidemic, but an effective non-invasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated by their peptide character. In order to overcome this unfavorable fact, we have applied the lipidization of neuropeptide prolactin-releasing peptide (PrRP), whose strong anorexigenic effect was demonstrated.