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Hypothalamic involvement in the beneficial effects of restricted diets on glucose tolerance in mice
Author(s) -
Minor Robin K,
Percival Susan S,
de Cabo Rafael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb41-b
Subject(s) - endocrinology , medicine , neuropeptide y receptor , orexigenic , monosodium glutamate , arcuate nucleus , knockout mouse , appetite , hypothalamus , neuropeptide , biology , receptor
Dietary restriction (DR) is the only consistent nutritional intervention that increases longevity while decreasing the incidence and onset of age‐related diseases and functional decline in various species. However, the mechanism of the DR effect remains unknown. Furthermore, while DR studies involve the manipulation of caloric intake they have not sought to control or eliminate the induction of hunger. The inability to account for the contribution of hunger to the effects of DR becomes more critical as evidence accumulates supporting the hypothesis that the neuroendocrine response to DR is the primary mechanism driving its beneficial systemic effects. If hunger is indeed a critical component of DRs immediate effects that triggers protective adaptations seen in DR, then examining the effects of DR under appetite suppression would provide a means for observing the role of hunger in the DR mechanism, the aim of this study. Two animal models were employed: Neuropeptide‐Y knockout mice (NPY, a major orexigenic peptide) and monosodium glutamate‐injected mice (MSG damages the arcuate nucleus, the ‘satiety center’ of the hypothalamus that coordinates feeding behavior). While the NPY‐knockout mice displayed equivalent feeding behavior and body composition compared with controls, the MSG‐injected mice were obese yet hypophagic. Furthermore, while the NPY‐knockout mice exhibited lower fasting glucose and glucose tolerance by oral glucose tolerance test following DR, the response was attenuated in the MSG‐injected animals. These data suggest at least some of the beneficial effects of DR rely on unimpaired arcuate nucleus activity but are not contingent on NPY expression. Funding: NIH Intramural Research Program.