Cognitive and hormonal regulation of appetite for food presented in the olfactory and visual modalities.

The ability to regulate appetite is essential to avoid food over-consumption. The desire for a particular food can be triggered by its odor before it is even seen. Using fMRI, we identify the neural systems modulated by cognitive regulation when experiencing appetizing food stimuli presented in both olfactory and visual modalities, while being hungry. Regulatory instruction modulated bids for food items and inhalation patterns. Distinct brain regions were observed for up and down appetite-regulation, respectively the dorsomedial prefrontal cortex (dmPFC) and dorsolateral PFC. Food valuation engaged the ventromedial PFC and bilateral striatum. Furthermore, we identified a neurobiological marker for successful appetite upregulation. Individuals with higher blood levels of ghrelin were better at exercising up-regulation, and engaged the dmPFC more. These findings characterize the neural circuitry regulating food consumption within the healthy population and highlight how cognitive regulation modulates olfactomotor measures of olfaction.

A methodological investigation of a flexible surface MRI coil to obtain functional signals from the human olfactory bulb.

BACKGROUND: Mammalian olfaction begins with transduction in olfactory receptors, continues with extensive processing in the olfactory bulb, and culminates in cortical representation. Most rodent studies on the functional neuroanatomy of olfaction have concentrated on the olfactory bulb, yet whether this structure is tuned only to basic chemical features of odorants or also to higher-order perceptual features is unclear. NEW METHOD: Whereas studies of the human brain can typically uncover involvement of higher-order feature extraction, this has not been possible in the case of the olfactory bulb, inaccessible to fMRI. The present study examined whether a novel method of acquisition using a facial coil could overcome this limitation. RESULTS: A series of experiments provided preliminary evidence of odor-driven responses in the human olfactory bulb, and found that these responses differed between individuals. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: The present preliminary technical achievement renders possible to design novel human odor fMRI studies by considering the olfactory system from the olfactory bulb to associative areas.

Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased Activity in Olfactory Cortex.

Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.

Pleasantness and trigeminal sensations as salient dimensions in organizing the semantic and physiological spaces of odors.

A major issue in human olfaction research is to characterize the main dimensions that organize the space of odors. The present study examines this question and shows that, beside pleasantness, trigeminal sensations, and particularly irritation, play an important role. These results were consistent along two different spaces constructed using semantic description and physiological responses to 105 odorants, smelled and described by human participants. Taken together, these findings suggest that salient trigeminal features, in conjunction with pleasantness, are involved in detecting relevant emotional stimuli, and modify the way organisms categorize smells. These results shed light on the importance of trigeminal sensitivity in the well-established defensive function of olfaction.

Multidimensional representation of odors in the human olfactory cortex.

What is known as an odor object is an integrated representation constructed from physical features, and perceptual attributes mainly mediated by the olfactory and trigeminal systems. The aim of the present study was to comprehend how this multidimensional representation is organized, by deciphering how similarities in the physical, olfactory and trigeminal perceptual spaces of odors are represented in the human brain. To achieve this aim, we combined psychophysics, functional MRI and multivariate representational similarity analysis. Participants were asked to smell odors diffused by an fMRI-compatible olfactometer and to rate each smell along olfactory dimensions (pleasantness, intensity, familiarity and edibility) and trigeminal dimensions (irritation, coolness, warmth and pain). An event-related design was implemented, presenting different odorants. Results revealed that (i) pairwise odorant similarities in anterior piriform cortex (PC) activity correlated with pairwise odorant similarities in chemical properties (P < 0.005), (ii) similarities in posterior PC activity correlated with similarities in olfactory perceptual properties (P <0.01), and (iii) similarities in amygdala activity correlated with similarities in trigeminal perceptual properties (P < 0.01). These findings provide new evidence that extraction of physical, olfactory and trigeminal features is based on specific fine processing of similarities between odorous stimuli in a distributed manner in the olfactory system. Hum Brain Mapp 37:2161-2172, 2016. © 2016 Wiley Periodicals, Inc.

Dissociated neural representations induced by complex and simple odorant molecules.

An important challenge in olfaction research is to understand how percepts relate to the molecular structure of stimuli. Previous psychophysical studies showed that, whereas structurally simple odorant molecules evoked a more uniform qualitative perception as revealed by the use of a small number of labels to describe their olfactory quality, more complex odorants evoked a larger variety of olfactory qualities, reflecting a more heterogeneous qualitative perception. The present study examined how this influence of odorant molecular complexity on perception is reflected in the human brain. To this end, participants were stimulated with structurally simple and complex odorant molecules and their brain responses were assessed by functional magnetic resonance imaging (fMRI). Low- and high-complexity odorants were judged to have the same intensity, pleasantness and familiarity (p>0.05 in all cases), whereas complex odorants induced more quality labels than simple odorants (p<0.02) as expected. Imaging analysis of complex vs. simple odorants revealed significant activation in dorsal anterior cingulate gyrus, but not in primary olfactory areas. Taken together, these findings suggest dissociated neural representations of uniform and heterogeneous olfactory perception, highlighting for the first time the impact of odorant complexity on activity of the cingulate gyrus.

Hypothalamic actions of apelin on energy metabolism: new insight on glucose homeostasis and metabolic disorders.

Hypothalamus is key area implicated in control of glucose homeostasis. This structure integrates nervous and peripheral informations to adapt a response modifying peripheral glucose utilization and maintaining energetic balance. Among peripheral signals, adipokines such as adiponectin and leptin are of special importance since deregulations of their actions are closely associated to metabolic disorders such as obesity and type 2 diabetes. During the past ten years, we have identified a new adipokine named apelin which has emerging role in the control of metabolism. The originality of the apelinergic system is to be largely represented in peripheral tissues (adipose tissue, intestine, etc.) and in the brain. Then, apelin is released by adipose tissue as all adipokines, but also present another crucial role as neurotransmitter in hypothalamic neurons. By acting in the whole body, apelin exerts pleiotropic actions and is now considered as a major determinant of physiological functions. Besides its general beneficial effects on peripheral targets, central action of apelin remains still a matter of debate. In this review, we have made a parallel between peripheral vs. central actions of apelin in term of signalization and effects. Then, we have focused our attention on hypothalamic apelin and its potential role in glucose metabolism and associated pathologies.

Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice.

AIMS/HYPOTHESIS: Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific G-protein-coupled receptors; its synthesis is modulated in obesity. We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis. Here, our aim was to test this hypothesis. METHODS: First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mg kg(-1) day(-1), i.p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice. Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425. RESULTS: In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion. These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i.p.). Inhibition of glucose-induced insulin secretion by LPA also occurred in isolated mouse islets. Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance. The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia. Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle. CONCLUSIONS/INTERPRETATION: Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.

Natural and recombinant fungal laccases for paper pulp bleaching.

Three laccases, a natural form and two recombinant forms obtained from two different expression hosts, were characterized and compared for paper pulp bleaching. Laccase from Pycnoporus cinnabarinus, a well known lignolytic fungus, was selected as a reference for this study. The corresponding recombinant laccases were produced in Aspergillus oryzae and A. niger hosts using the lacI gene from P. cinnabarinus to develop a production process without using the expensive laccase inducers required by the native source. In flasks, production of recombinant enzymes by Aspergilli strains gave yields close to 80 mg l(-1). Each protein was purified to homogeneity and characterized, demonstrating that the three hosts produced proteins with similar physico-chemical properties, including electron paramagnetic resonance spectra and N-terminal sequences. However, the recombinant laccases have higher Michaelian (Km) constants, suggesting a decrease in substrate/enzyme affinity in comparison with the natural enzyme. Moreover, the natural laccase exhibited a higher redox potential (around 810 mV), compared with A. niger (760 mV) and A. oryzae (735 mV). Treatment of wheat straw Kraft pulp using laccases expressed in P. cinnabarinus or A. niger with 1-hydroxybenzotriazole as redox mediator achieved a delignification close to 75%, whereas the recombinant laccase from A. oryzae was not able to delignify pulp. These results were confirmed by thioacidolysis. Kinetic and redox potential data and pulp bleaching results were consistent, suggesting that the three enzymes are different and each fungal strain introduces differences during protein processing (folding and/or glycosylation).

EPR spectroscopy: a powerful technique for the structural and functional investigation of metalloproteins.

Numerous metal centers in proteins can be prepared in a redox state in which their ground state is paramagnetic. Complementary data provided by EPR, Mössbauer, electron nuclear double resonance, magnetic circular dichroism, and NMR spectroscopies have therefore played a major role in the elucidation of the structure and function of these centers. Among those techniques the most commonly used is certainly EPR spectroscopy. In this article various aspects of the current applications of EPR to the structural and functional study of metalloproteins are presented. They are illustrated by recent studies carried out in our laboratory in the field of metalloenzymes and electron transfer systems. The power of numerical simulation techniques is emphasized throughout this work.

Nature and electronic structure of the Ni-X dinuclear center of Desulfovibrio gigas hydrogenase. Implications for the enzymatic mechanism.

The recent determination of the X-ray crystal structure of Desulfovibrio gigas hydrogenase has revealed that the active site is a Ni-X dinuclear center [Volbeda, A., Charon, M. H., Piras, C., Hatchikian, E. C., Frey, M., & Fontecilla-Camps, J. C. (1995) Nature 373, 580-587]. This unexpected result calls for a re-examination of the magnetic and redox properties that have been attributed previously to a mononuclear Ni center. We have used a combination of dosimetric and electron paramagnetic resonance (EPR) techniques to investigate the nature and the electronic structure of the Ni-X center in the redox forms of D. gigas hydrogenase giving EPR signals. The metal atom X was first shown to be Fe by accurate metal content analyses. Next, by determining the EPR characteristics of a polycrystal powder, it was shown that the redox form of the enzyme studied in the X-ray crystal experiments was essentially Ni-A. The temperature dependence of the Ni-A, Ni-B, Ni-C, and Ni-L EPR signals was studied over a large temperature range. No deviation from Curie's law could be detected, which places strong constraints upon the magnitude of the possible magnetic interactions between the Ni and Fe centers. When these results and the other available magnetic data are analyzed in the light of the crystal structure, it is concluded that the Fe center is diamagnetic in all the redox states of the enzyme. On the basis of these results, a mechanistic scheme consistent with a large body of experimental data can be proposed for Ni-containing hydrogenases.

Structural organization of the Ni and (4Fe-4S) centers in the active form of Desulfovibrio gigas hydrogenase. Analysis of the magnetic interactions by electron paramagnetic resonance spectroscopy.

The Desulfovibrio gigas hydrogenase is a typical (NiFe) hydrogenase containing a Ni center and three FeS centers, one [3Fe-4S] and two [4Fe-4S] clusters. When the enzyme is activated under hydrogen gas, the Ni center becomes paramagnetic, giving a characteristic electron paramagnetic resonance (EPR) signal with g values at 2.19, 2.14 and 2.01, the Ni-C signal. Two redox states of the enzyme can be prepared, in which the [4Fe-4S] clusters are either diamagnetic or paramagnetic. In this latter state, the magnetic coupling between metal centers induces both the appearance at low temperature of a complex EPR spectrum, the split Ni-C signal, and a significant enhancement of the relaxation rates of the Ni center. Good simulations of the split Ni-C signal recorded at three different microwave frequencies (X-band, Q-band, and S-band) are obtained by using a model based on a point dipole approximation of the dipolar and exchange interactions between paramagnets. The spectral analysis demonstrates that only one [4Fe-4S]1+ cluster is significantly coupled to the Ni site and provides a detailed description of the relative arrangement of the two centers. In addition, the magnetic characteristics of this [4Fe-4S]1+ cluster can be deduced from the simulations. Moreover, the spin-spin and spin-lattice relaxation times of the interacting centers were measured in the two redox states of the enzyme, either by power saturation and pulsed EPR experiments at low temperature or from the broadening of the EPR lines at higher temperature. The relaxation behavior of the Ni center is well explained by using in the theoretical analysis, the set of structural and magnetic parameters deduced from the spectral simulations. Our structural conclusions on the active D. gigas hydrogenase are compared to the preliminary data of a low-resolution crystal structure of the oxidized enzyme [Volbeda, A., Piras, C., Charon, M. H., Hatchikian, E. C., Frey, M., & Fontecilla-Camps, J. C. (1993) News Lett. Protein Crystallogr. 28, 30-33].