A sensitive period for environmental regulation of eating behavior and leptin sensitivity

Laboratory of Neurobiology, Scuola Normale Superiore, 56100 Pisa, Italy.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2010; 107(38):16673-8. DOI: 10.1073/pnas.0911832107
Source: PubMed


Western lifestyle contributes to body weight dysregulation. Leptin down-regulates food intake by modulating the activity of neural circuits in the hypothalamic arcuate nucleus (ARC), and resistance to this hormone constitutes a permissive condition for obesity. Physical exercise modulates leptin sensitivity in diet-induced obese rats. The role of other lifestyle components in modulating leptin sensitivity remains elusive. Environmentally enriched mice were used to explore the effects of lifestyle change on leptin production/action and other metabolic parameters. We analyzed adult mice exposed to environmental enrichment (EE), which showed decreased leptin, reduced adipose mass, and increased food intake. We also analyzed 50-d-old mice exposed to either EE (YEE) or physical exercise (YW) since birth, both of which showed decreased leptin. YEE mice showed no change in food intake, increased response to leptin administration, increased activation of STAT3 in the ARC. The YW leptin-induced food intake response was intermediate between young mice kept in standard conditions and YEE. YEE exhibited increased and decreased ratios of excitatory/inhibitory synapses onto α-melanocyte-stimulating hormone and agouti-related peptide neurons of the ARC, respectively. We also analyzed animals as described for YEE and then placed in standard cages for 1 mo. They showed no altered leptin production/action but demonstrated changes in excitatory/inhibitory synaptic contacts in the ARC similar to YEE. EE and physical activity resulted in improved insulin sensitivity. In conclusion, EE and physical activity had an impact on feeding behavior, leptin production/action, and insulin sensitivity, and EE affected ARC circuitry. The leptin-hypothalamic axis is maximally enhanced if environmental stimulation is applied during development.

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Available from: Gaia Scabia, Feb 28, 2014
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    • "The effect of EE on local LFP activity in V1 and A1 and on corticocortical interactions between these two primary sensory cortices pointed to neural plasticity phenomena (Bavelier and Neville, 2002). We looked for a molecular correlate of functional changes by analyzing the expression of vGluT-1 and vGAT, which are reliable markers to probe the global excitatory and inhibitory tones of the brain (Mainardi et al., 2010a,b). It is worth noting that changes in intracortical inhibition have been associated also with physiological brain aging. "
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    ABSTRACT: Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.
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    • "Since the animals usually experience a rebound feeding the day after fasting, the total caloric balance, also in this case, is usually reduced to 70–90% of normal intake [45] [46]. More recently, environmental enrichment (EE) has been added to this list [47]. Compared to the simple physical exercise protocol, EE adds cognitive, sensory, and social stimulations by means of rearing larger groups of animals (up to ten, compared to the usual three to five) in wider cages with several objects to explore that are frequently changed [48] [49]. "
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    • "Moreover, the mice were fed ad libitum throughout this study, and training did not increase caloric intake within each diet. Again, this validates the moderate intensity level of the exercise intervention, as exercise protocols that are strenuous enough to produce weight loss generally result in an increase in voluntary energy intake [12, 13]. "
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