Mitral Cells of the Olfactory Bulb Perform Metabolic Sensing and Are Disrupted by Obesity at the Level of the Kv1.3 Ion Channel

Sixty-five percent of Americans are over-weight. While the neuroendocrine controls of energy homeostasis are well known, how sensory systems respond to and are impacted by obesity is scantily understood. The main accepted function of the olfactory system is to provide an internal depiction of our external chemical environment, starting from the detection of chemosensory cues. We hypothesized that the system additionally functions to encode internal chemistry via the detection of chemicals that are important indicators of metabolic state. We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3. Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application. Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice. Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation. Mice that were chronically administered insulin using intranasal delivery approaches exhibited either an elevation in basal firing frequency or fired a single cluster of action potentials. Following chronic administration of the hormone, mitral cells were inhibited by application of acute insulin rather than excited. Mice made obese through a diet of ∼32% fat exhibited prominent changes in mitral cell action potential shape and clustering behavior, whereby the subsequent response to acute insulin stimulation was either attenuated or completely absent. Our results implicate an inappropriate neural function of olfactory sensors following exposure to chronic levels of the hormone insulin (diabetes) or increased body weight (obesity)

Endocannabinoids selectively enhance sweet taste

Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB1 receptors in hypothalamus and limbic forebrain to induce appetite and stimulate food intake. Circulating endocannabinoid levels inversely correlate with plasma levels of leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors. Recently, taste has been found to be a peripheral target of leptin. Leptin selectively suppresses sweet taste responses in wild-type mice but not in leptin receptor-deficient db/db mice. Here, we show that endocannabinoids oppose the action of leptin to act as enhancers of sweet taste. We found that administration of AEA or 2-AG increases gustatory nerve responses to sweeteners in a concentration-dependent manner without affecting responses to salty, sour, bitter, and umami compounds. The cannabinoids increase behavioral responses to sweet-bitter mixtures and electrophysiological responses of taste receptor cells to sweet compounds. Mice genetically lacking CB1 receptors show no enhancement by endocannnabinoids of sweet taste responses at cellular, nerve, or behavioral levels. In addition, the effects of endocannabinoids on sweet taste responses of taste cells are diminished by AM251, a CB1 receptor antagonist, but not by AM630, a CB2 receptor antagonist. Immunohistochemistry shows that CB1 receptors are expressed in type II taste cells that also express the T1r3 sweet taste receptor component. Taken together, these observations suggest that the taste organ is a peripheral target of endocannabinoids. Reciprocal regulation of peripheral sweet taste reception by endocannabinoids and leptin may contribute to their opposing actions on food intake and play an important role in regulating energy homeostasis

Seaweeds for umami flavour in the New Nordic Cuisine

<p>Abstract</p> <p>Use of the term 'umami' for the fifth basic taste and for describing the sensation of deliciousness is finding its way into Western cuisine. The unique molecular mechanism behind umami sensation is now partly understood as an allosteric action of glutamate and certain 5'-ribonucleotides on the umami receptors. Chefs have started using this understanding to create dishes with delicious taste by adding old and new ingredients that enhance umami. In this paper, we take as our starting point the traditional Japanese soup broth <it>dashi </it>as the 'mother' of umami and demonstrate how <it>dashi </it>can be prepared from local, Nordic seaweeds, in particular the large brown seaweed sugar kelp (<it>Saccharina latissima</it>) and the red seaweed dulse (<it>Palmaria palmata</it>), possibly combined with bacon, chicken meat or dried mushrooms to provide synergy in the umami taste. Optimal conditions are determined for <it>dashi </it>extraction from these seaweeds, and the corresponding glutamate, aspartate and alaninate contents are determined quantitatively and compared with Japanese <it>dashi </it>extracted from the brown seaweed <it>konbu </it>(<it>Saccharina japonica</it>). Dulse and <it>dashi </it>from dulse are proposed as promising novel ingredients in the New Nordic Cuisine to infuse a range of different dishes with umami taste, such as ice cream, fresh cheese and bread.</p