sensitive period for environmental regulation of eating behavior and leptin sensitivity
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 sen...
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Mainardi, Marco Scabia, Gaia Vottari, Teresa Santini, Ferruccio Pinchera, Aldo Maffei, Lamberto Pizzorusso, Tommaso Maffei, Margherita |
| description | 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. |
| doi_str_mv | 10.1073/pnas.0911832107 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0911832107</identifier><identifier>PMID: 20823242</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animal feeding behavior ; Animals ; Arcuate Nucleus of Hypothalamus - physiology ; Biological Sciences ; body weight ; Eating - physiology ; Environment ; environmental regulations ; Exercise ; Feeding Behavior - physiology ; Food intake ; Gene Expression ; Hormones ; Humans ; insulin ; Insulin Resistance - physiology ; Leptin - physiology ; Lifestyles ; Male ; Metabolism ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Motor Activity - physiology ; Neurons ; Obesity ; Obesity - etiology ; Obesity - physiopathology ; Peptides ; physical activity ; Post hoc ; Rats ; Rodents ; Sensitivity ; Signal Transduction ; STAT3 Transcription Factor - physiology ; Synapses ; T tests</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-09, Vol.107 (38), p.16673-16678</ispartof><rights>Copyright National Academy of Sciences Sep 21, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-fd1c6e0c8a1d9f7717fabc6b9b2ff537eff6f82dee01b39791b74f1e32d4ccfd3</citedby><cites>FETCH-LOGICAL-c620t-fd1c6e0c8a1d9f7717fabc6b9b2ff537eff6f82dee01b39791b74f1e32d4ccfd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/38.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20779725$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20779725$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20823242$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mainardi, Marco</creatorcontrib><creatorcontrib>Scabia, Gaia</creatorcontrib><creatorcontrib>Vottari, Teresa</creatorcontrib><creatorcontrib>Santini, Ferruccio</creatorcontrib><creatorcontrib>Pinchera, Aldo</creatorcontrib><creatorcontrib>Maffei, Lamberto</creatorcontrib><creatorcontrib>Pizzorusso, Tommaso</creatorcontrib><creatorcontrib>Maffei, Margherita</creatorcontrib><title>sensitive period for environmental regulation of eating behavior and leptin sensitivity</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Animal feeding behavior</subject><subject>Animals</subject><subject>Arcuate Nucleus of Hypothalamus - physiology</subject><subject>Biological Sciences</subject><subject>body weight</subject><subject>Eating - physiology</subject><subject>Environment</subject><subject>environmental regulations</subject><subject>Exercise</subject><subject>Feeding Behavior - physiology</subject><subject>Food intake</subject><subject>Gene Expression</subject><subject>Hormones</subject><subject>Humans</subject><subject>insulin</subject><subject>Insulin Resistance - physiology</subject><subject>Leptin - physiology</subject><subject>Lifestyles</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Animal</subject><subject>Motor Activity - physiology</subject><subject>Neurons</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - physiopathology</subject><subject>Peptides</subject><subject>physical activity</subject><subject>Post hoc</subject><subject>Rats</subject><subject>Rodents</subject><subject>Sensitivity</subject><subject>Signal Transduction</subject><subject>STAT3 Transcription Factor - physiology</subject><subject>Synapses</subject><subject>T tests</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkstv1DAQxiMEokvhzAmwuHBKO34kti9IqOIlVeIAFUfLScZbr7L2Yicr9b_H0W4fcIGT7ZnffJoZf1X1ksIZBcnPd8HmM9CUKs5K4FG1ouVVt0LD42oFwGStBBMn1bOcNwCgGwVPqxMGinEm2Kr6mTFkP_k9kh0mHwfiYiIY9j7FsMUw2ZEkXM-jnXwMJDqC5RbWpMNru_eFtWEgI-5KkNxq-enmefXE2THji-N5Wl19-vjj4kt9-e3z14sPl3XfMphqN9C-ReiVpYN2UlLpbNe3ne6Ycw2X6FzrFBsQgXZcS007KRxFzgbR927gp9X7g-5u7rY49KXjZEezS35r042J1ps_M8Ffm3XcG6aFkJwXgXdHgRR_zZgns_W5x3G0AeOcjWpa2Uim2f-RDQf9T7JgVCsFTSHf_kVu4pxC2dgCgaCiFQU6P0B9ijkndHfjUTCLDcxiA3Nvg1Lx-uFW7vjbfy8AOQJL5b2cNFwZ2rZyWcyrA7LJU0wPJKTUki2tvznknY3GrpPP5uo7A8qBKs2oBP4bsKnONg</recordid><startdate>20100921</startdate><enddate>20100921</enddate><creator>Mainardi, Marco</creator><creator>Scabia, Gaia</creator><creator>Vottari, Teresa</creator><creator>Santini, Ferruccio</creator><creator>Pinchera, Aldo</creator><creator>Maffei, Lamberto</creator><creator>Pizzorusso, Tommaso</creator><creator>Maffei, Margherita</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7ST</scope><scope>7U6</scope><scope>5PM</scope></search><sort><creationdate>20100921</creationdate><title>sensitive period for environmental regulation of eating behavior and leptin sensitivity</title><author>Mainardi, Marco ; 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>20823242</pmid><doi>10.1073/pnas.0911832107</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animal feeding behavior Animals Arcuate Nucleus of Hypothalamus - physiology Biological Sciences body weight Eating - physiology Environment environmental regulations Exercise Feeding Behavior - physiology Food intake Gene Expression Hormones Humans insulin Insulin Resistance - physiology Leptin - physiology Lifestyles Male Metabolism Mice Mice, Inbred C57BL Models, Animal Motor Activity - physiology Neurons Obesity Obesity - etiology Obesity - physiopathology Peptides physical activity Post hoc Rats Rodents Sensitivity Signal Transduction STAT3 Transcription Factor - physiology Synapses T tests |
| title | sensitive period for environmental regulation of eating behavior and leptin sensitivity |
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