ABSTRACT
Kokumi taste is a well-accepted and characterised taste modality and is described as a sensation of enhancement of sweet, salty, and umami tastes. The Calcium Sensing Receptor (CaSR) has been designated as the putative kokumi taste receptor for humans, and a number of kokumi-active ligands of CaSR have been discovered recently with activity confirmed both in vivo and in vitro. Domestic cats (Felis catus) are obligate carnivores and accordingly, their diet is abundant in proteins, peptides, and amino acids. We hypothesised that CaSR is a key taste receptor for carnivores, due to its role in the detection of different peptides and amino acids in other species. Using in silico, in vitro and in vivo approaches, here we compare human CaSR to that of a model carnivore, the domestic cat. We found broad similarities in ligand specificity, but differences in taste sensitivity between the two species. Indeed our in vivo data shows that cats are sensitive to CaCl2 as a kokumi compound, but don't show this same activity with Glutathione, whereas for humans the reverse is true. Collectively, our data suggest that kokumi is an important taste modality for carnivores that drives the palatability of meat-derived compounds such as amino acids and peptides, and that there are differences in the perception of kokumi taste between carnivores and omnivores.
Subject(s)
Cats/physiology , Taste Perception , Amino Acid Sequence , Amino Acids/analysis , Animals , Calcium Chloride/metabolism , Glutathione/metabolism , Humans , Ligands , Magnesium Chloride/metabolism , Meat Products/analysis , Peptides/analysis , Protein Binding , Receptors, Calcium-Sensing/metabolism , Taste Buds/metabolismABSTRACT
Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2(tm1a/tm1a)) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2(tm1a/tm1a) mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2(tm1a/tm1a) mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Cholesterol/blood , Energy Metabolism/genetics , Receptor Activity-Modifying Proteins/metabolism , Repressor Proteins/metabolism , Adaptor Proteins, Signal Transducing , Animals , Anxiety/genetics , Anxiety/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Behavior, Animal/physiology , Body Weight/genetics , Corticotropin-Releasing Hormone/genetics , Corticotropin-Releasing Hormone/metabolism , Eating/genetics , Lipid Metabolism/genetics , Mice , Mice, Knockout , Motor Activity/genetics , Neurons/metabolism , Oxytocin/genetics , Oxytocin/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Receptor Activity-Modifying Proteins/genetics , Repressor Proteins/genetics , Thyrotropin-Releasing Hormone/genetics , Thyrotropin-Releasing Hormone/metabolismABSTRACT
Frequency-selective bolometers (FSBs) are a new type of detector for millimeter and submillimeter wavelengths that are transparent to all but a narrow range of frequencies as set by characteristics of the absorber itself. Therefore stacks of FSBs tuned to different frequencies provide a low-loss compact method for utilizing a large fraction of the light collected by a telescope. Tests of prototype FSBs indicate that the absorption spectra are well predicted by models, that peak absolute absorption efficiencies of the order of 50% are attainable, and that their out-of-band transmission is high.