The human gastrointestinal tract (GIT) is inhabited by a wide cluster of microorganisms that play protective, structural, and metabolic functions for the intestinal mucosa. Gut microbiota is involved in the barrier functions and in the maintenance of its homeostasis. It provides nutrients, participates in the signaling network, regulates the epithelial development, and affects the immune system. Considering the microbiota ability to respond to homeostatic and physiological changes, some researchers proposed that it can be seen as an endocrine organ. Evidence suggests that different factors can determine changes in the gut microbiota. These changes can be both quantitative and qualitative resulting in variations of the composition and metabolic activity of the gut microbiota which, in turn, can affect health and different disease processes. Recent studies suggest that exercise can enhance the number of beneficial microbial species, enrich the microflora diversity, and improve the development of commensal bacteria. All these effects are beneficial for the host, improving its health status. In this paper, we intend to shed some light over the recent knowledge of the role played by exercise as an environmental factor in determining changes in microbial composition and how these effects could provide benefits to health and disease prevention.

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Exercise Modifies the Gut Microbiota with Positive Health Effects

The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behaviour, energy homeostasis, reward systems, cognition and mood Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions The selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood Conversely, orexin deficiency results in learning and memory deficits, and depression

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Orexin System: The Key for a Healthy Life

Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats

Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field. Cloning of cannabinoid receptors in the 90s and the identification of the endogenous mediators arachidonylethanolamide (anandamide, AEA) and 2-arachidonyglycerol (2-AG), led to the characterization of the endocannabinoid system (ECS), together with their metabolizing enzymes and membrane transporters. Today, the ECS is known to be involved in diverse functions such as appetite control, food intake, energy balance, neuroprotection, neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain, inflammatory responses, as well as in cancer therapy. Western diet as well as restriction of micronutrients and fatty acids, such as DHA, could be related to altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs, contributing to the progression of cardiovascular diseases, diabetes, obesity, depression or impairing conditions, such as Alzheimer' s disease. Here we review how diets based in PUFAs might be linked to ECS and to the maintenance of central and peripheral metabolism, brain plasticity, memory and learning, blood flow, and genesis of neural cells.

Polyunsaturated fatty acids and endocannabinoids in health and disease.

The basal forebrain cholinergic system is considered as a major component of attentive mediator system. It could be activated by different ingoing inputs, and among them the hypothalamus represents an important source of projections and the orexin neurons, whose cell bodies are present in the lateral hypothalamus, highly contribute to these projections. Recently, the orexin-producing neurons have been considered to act in the basal forebrain promoting arousal and attention. Aim of the present review is trying to explain the putative effects of orexin-producing neurons and their projection to the basal forebrain in order to support the hypothesis that orexin system may contribute to attentional processing toward increased cell activity and cortical acetylcholine (Ach) release. Collectively, the available data seem to support this hypothesis: orexins excite cholinergic neurons increasing acetylcholine release in cerebral cortex contributing to cerebral cortical activation and prefrontal cortex associated with executive system. We have reviewed evidence suggesting that the BF may be a key target through which orexin neurons promote attention.

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Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention.

It is extremely important for the health to understand the regulatory mechanisms of energy expenditure. These regulatory mechanisms play a central role in the pathogenesis of body weight alteration. The hypothalamus integrates nutritional information derived from all peripheral organs. This region of the brain controls hormonal secretions and neural pathways of the brainstem. Orexin-A is a hypothalamic neuropeptide involved in the regulation of feeding behavior, sleep-wakefulness rhythm, and neuroendocrine homeostasis. This neuropeptide is involved in the control of the sympathetic activation, blood pressure, metabolic status, and blood glucose level. This minireview focuses on relationship between the sympathetic nervous system and orexin-A in the control of eating behavior and energy expenditure. The “thermoregulatory hypothesis” of food intake is analyzed, underlining the role played by orexin-A in the control of food intake related to body temperature. Furthermore, the paradoxical eating behavior induced orexin-A is illustrated in this minireview.

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Amelia Dato

Papers

Orexin-A controls sympathetic activity and eating behavior.