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In most species, food intake is influenced by olfactory cues and metabolic status can affect the olfactory function of animals and regulate feeding-related behaviors. We investigated whether modulation of the endocrine system that regulates or modifies energy balance affected the olfactory system by examining four rat strains, obese Zucker and obesity-resistant Lou/C rats and their counterparts. Such models were chosen because they differ largely in their energy status and in their insulin and leptin blood levels, two hormones known to impact olfactory behaviors. After evaluation of the main metabolic parameters, we analyzed the food-driven olfactory behaviors of the four strains by measuring general activity time and sniffing time in response to food cues together with food reward localization performances in fed and fasted states. In fed conditions, obese Zucker and Wistar rats exhibited a great interest for food odor, which was not enhanced by fasting, in contrast to Lou/C and Zucker lean rats. All strains, except Lou/C, showed decreased latencies to find a hidden food reward with time, whereas a 24-h fasting was necessary to improve food search performances in Lou/C. These metabolic and behavioral changes were partly associated with variations in the transcription profiles of leptin, insulin and orexin and their receptors in the hypothalamus and olfactory system. The results show that variations in metabolic-related genes expression along the olfactory pathways comes with obesity in influencing food odors-driven behaviors. Our data indicate that food-olfactory driven behaviors are clearly affected by the long-term metabolic status., (Copyright © 2014 Elsevier B.V. All rights reserved.)

All olfactory epithelium cells, including rapidly self-renewing olfactory sensory neurons (OSN), are continuously subjected to external airborne aggressions. We hypothesized that the apical part of rat olfactory epithelia (AOE) could be the site of a local translation to be able to respond rapidly to external stimuli. We purified significant amounts of mRNAs from AOE. Sequencing of the cDNA library identified 348 mRNA species. Of these, the 220 AOE transcripts encoding proteins with known biological functions were classified in functional groups. The main functional class (40%) coded for defense, detoxification, anti-oxidant stress and innate immunity. Other classes comprised mRNAs encoding functions for neuronal metabolism and life (19%), nuclear transcription control (15%), cell survival and proliferation (13%), RNA processing and translation (12%). They did not contain any known members of the olfactory transduction pathway. The expression of a sub-set of AOE transcripts was investigated in sub-cellular AOE fractions highly enriched in ciliated dendrites and in AOE fractions after forced hemilateral OSN-specific degeneration. All the mRNAs tested were found to be: i) present in enriched ciliated dendrite preparations ii) down-regulated after OSN degeneration iii) co-purified with polysomal fractions, suggesting their commitment to local translation. We provide strong evidence that the extreme apical side of the olfactory epithelium expresses a unique transcriptome, whose function is not related to olfaction but mainly to defense and survival. The possible local translation of this transcriptome is demonstrated, in supporting cells as well as in olfactory neuron ciliated dendrites., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Leptin is an adipocyte-derived cytokine that regulates body weight mainly via the long form of the leptin receptor (Ob-Rb). Leptin and its receptors are expressed in several tissues, suggesting that leptin might also be effective peripherally. We hypothesized that, as shown in taste cells, leptin and its receptors isoforms (Ob-Rs) could be present in the rat olfactory mucosa (OM). Using RT-PCR, light and electron microscopy immunohistochemistry (ICC), we found that different isoforms of the receptor were expressed in OM and localized in sustentacular cells and in a subpopulation of maturating neurons; in addition, immunoreactivity was also present in differentiated neurons and enriched at the cilia membranes, where the odorants bind to their receptors. Moreover, using RT-PCR, ICC and RIA measurements, we showed that leptin is synthesized locally in the olfactory mucosa. In addition, we demonstrate that fasting causes a significant enhanced transcription of both leptin and Ob-Rs in rat OM by quantitative RT-PCR data. Altogether, these results strongly suggested that leptin, acting as an endocrine or a paracrine factor, could be an important regulator of olfactory function, as a neuromodulator of the olfactory message in cilia of mature olfactory receptors neurons (ORN), but also for the homeostasis of this complex tissue, acting on differentiating neurons and on sustentacular cells.

Orexin-A and -B, also known as hypocretins, are two neuropeptides acting on feeding and sleep. They are specific ligands for two different receptors belonging to the G-protein coupled receptors family. Orexin fibers and orexin receptor neurons have been previously described in the forebrain olfactory system. Using immunocytochemistry, we showed that both orexin-A and -B as well as their receptors were present at different levels of the olfactory system, from the nasal mucosa to nuclei of the amygdala. A punctuated staining for orexins and their receptors was detected at the apical part of the olfactory epithelium; in the lamina propria of the mucosa, the staining was localized around olfactory nerves. At the ultrastructural level, olfactory neurons and supporting cells were found immunoreactive for orexins and their receptors. The labeling was localized in dendritic knobs and cilia of neurons, in the apical part and microvilli of supporting cells. The finding of immunolabeled cisternae of reticulum strongly suggests a local synthesis of both peptides and receptors, confirmed by RT-PCR experiments. In forebrain and amygdala regions, we detected numerous orexin fibers. Orexin receptors were present in mitral-tufted cells of the bulb and in many neuronal perikarya in the anterior olfactory nuclei, piriform cortex and amygdala nuclei. Altogether, these results show that orexins and their receptors are present at all levels of the olfactory system, from cilia where odors bind to their receptors to central regions where integration of olfactory signals occurs. They suggest a possible modulation of olfactory perception by these neuropeptides.