Persistent alterations in neuropeptide Y release in the paraventricular nucleus of rats subjected to dietary manipulation during early life

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Abstract
The aim of the present experiment was to determine the influence of nutritional manipulations during early life on feeding regulatory mechanisms. For this purpose, neuropeptide Y (NPY) release in the hypothalamic paraventricular nucleus was measured in male offspring born to dams fed either on a control (C) diet, on a high-carbohydrate (HC) diet or on a high-fat (HF) diet during gestation and lactation periods. In addition, we examined the development of dietary preferences in these rats. NPY release was measured in vivo through the push-pull technique after a stimulation with 2-deoxy-glucose (2DG), a blocker of carbohydrate metabolism. NPY release was significantly enhanced in the HC rats after 2DG (+89% vs. control and +54% vs. HF rats; P < 0.01). In a two-bottle choice test, a clear preference for carbohydrate (62% vs. 38%; P < 0.01) was present as early as 30 days of age in control rats. The establishment of this preference in HC and HF rats was delayed by 2 and 3 months, respectively. Therefore, each type of dietary manipulation during early life has left a specific imprint in the offspring. The change in reactivity of the NPY system to glucopenia persisted in adulthood. When combined with the early changes in the dietary preferences, this can lead to adverse effects on body weight when abundant and palatable food is offered. These data support the hypothesis of an intrauterine and perinatal programming of the central regulatory mechanisms and reinforce the necessity of a preventive approach for the treatment of obesity and related metabolic disorders.