Neuroscience
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Central oxytocin potently reduces food intake and is being pursued as a clinical treatment for obesity. While sexually dimorphic effects have been described for the effects of oxytocin on several behavioral outcomes, the role of sex in central oxytocin modulation of feeding behavior is poorly understood. Here we investigated the effects of sex, estrous cycle stage, and female sex hormones (estrogen, progesterone) on central oxytocin-mediated reduction of food intake in rats. ⋯ Indeed, additional results reveal that estrogen, but not progesterone replacement, in ovariectomized rats abolishes oxytocin-mediated reductions in chow intake. Lastly, oxytocin receptor mRNA (Oxtr) quantification (via quantitative PCR) and anatomical localization (via fluorescent in situ hybridization) in previously established sites of action for oxytocin control of food intake revealed comparable Oxtr expression between male and female rats, suggesting that observed sex and estrous differences may be based on variations in ligand availability and/or binding. Overall, these data show that estrogen reduces the effectiveness of central oxytocin to inhibit food intake, suggesting that sex hormones and estrous cycle should be considered in clinical investigations of oxytocin for obesity treatment.
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Social interaction is important for survival in most social species including humans. To ensure social activities, individuals experience reward from social interaction, generating a powerfully reinforcing process. Here we hypothesized that reward from social interaction in a juvenile male rat pair may be enhanced by ghrelin, a circulating hormone that has been shown to enhance reward from other natural (e.g. food, sex) as well as artificial reinforcers (e.g. alcohol and other drugs of abuse). ⋯ We found that ghrelin increased and a ghrelin antagonist decreased preference for social interaction, but only in the heavier partner in a social pair. In addition, we found that administered ghrelin induced a positive association between preference for social interaction and body weight difference within socially interacting pairs, where larger ghrelin treated rats preferred social interaction, whereas smaller ghrelin treated rats avoided it, which raises the question if ghrelin could have a role in implementing social hierarchies in rats. In summary, we conclude that ghrelin signaling increases the reward from social interaction in a manner that reflects the degree of divergence in body weight between the social pair.
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The aim of this study was to indentify the involvement of leptin receptors (LepR) in astrocytes in hippocampal synaptic transmission and plasticity and metabolism. To this end we used a genetic mouse model (GFAP-LepR-/-) of specific LepR ablation in GFAP positive cells and recorded excitatory postsynaptic potentials (fEPSPs) within the CA1 area. Glutamate (Glu) uptake and the expression of Glu transporters (EEAT3, GLT-1 and GLAST) and enzymes involved in Glu metabolism (glutamine synthase, GABA decarboxylase 65 and 67) were quantified. ⋯ Hippocampal slices from GFAP-LepR-/- mice displayed lower Glu uptake efficacy together with up-regulation of GLT-1, glutamine synthase, GFAP and GLUT-1. In conclusion, astrocyte LepRs are involved in the maintenance of Glu homeostasis and Glu neurotransmission within the hippocampus. Our findings support a role of hippocampal LepRs in synaptic plasticity, which could have an impact on memory and learning processes.
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The study of consummatory responses during food intake represents a unique opportunity to investigate the physiological, psychological and neurobiological processes that control ingestive behavior. Recording the occurrence and temporal organization of individual licks across consumption, also called lickometry, yields a rich data set that can be analyzed to dissect consummatory responses into different licking patterns. These patterns, divided into trains of licks separated by pauses, have been used to deconstruct the many influences on consumption, such as palatability evaluation, incentive properties, and post-ingestive processes. ⋯ We then discuss how licking patterns can be used to investigate the impact of different physiological need states on processes governing ingestive behavior. We also present new data showing how licking patterns are changed in an animal model of protein appetite and how this may guide food choice in different protein-associated hedonic and homeostatic states. Thus, recording lick microstructure can be achieved relatively easily and represents a useful tool to provide insights, beyond the measurement of total intake, into the multiple factors influencing ingestive behavior.
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Review
Immunometabolic Changes in Glia - A Potential Role in the Pathophysiology of Obesity and Diabetes.
Chronic low-grade inflammation is a feature of the pathophysiology of obesity and diabetes in the CNS as well as peripheral tissues. Glial cells are critical mediators of the response to inflammation in the brain. Key features of glia include their metabolic flexibility, sensitivity to changes in the CNS microenvironment, and ability to rapidly adapt their function accordingly. ⋯ Inflammation is an energetically expensive process that requires adaptive changes in cellular metabolism and, in turn, metabolic intermediates can also have immunomodulatory actions. Such "immunometabolic" changes in peripheral immune cells have been implicated in contributing to disease pathology in obesity and diabetes. This review will discuss the evidence for a role of immunometabolic changes in glial cells in the systemic regulation of energy and glucose homeostasis, and how this changes in the context of obesity and diabetes.