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

Marco Mainardi, G Scabia, T Vottari, F Santini, A Pinchera, L Maffei, T Pizzorusso, M. Maffei

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

33 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)16673-16678
Numero di pagine6
RivistaProceedings of the National Academy of Sciences of the United States of America
Volume107
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Animals
  • Arcuate Nucleus
  • Eating
  • Environment
  • Feeding Behavior
  • Gene Expression
  • Humans
  • Insulin Resistance
  • Leptin
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Motor Activity
  • Obesity
  • STAT3 Transcription Factor
  • Signal Transduction

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