Feeding patterns are important factors in obesity evolvement. Time-restricted feeding schedules (tRF) during resting phase change energy homeostasis regulation, disrupting the circadian release of metabolism-regulating hormones, such as leptin, insulin and corticosterone and promoting body weight gain. Thyroid (HPT) and adrenal (HPA) axes exhibit a circadian regulation and are involved in energy expenditure, thus studying their parameters in tRF paradigms will elucidate their role in energy homeostasis impairments under such conditions. As tRF in young animals is poorly studied, we subjected prepuberal rats to a tRF either in light (LPF) or in darkness phase (DPF) and analyzed HPT and HPA response when they reach adulthood, as well as their arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei neurons’ sensitivity to leptin in subsets of 10-week-old animals after fasting and with i.p. leptin treatment. LPF group showed high body weight and food intake, along with increased visceral fat pads, corticosterone, leptin and insulin serum levels, whereas circulating T₄ decreased. HPA axis hyperactivity was demonstrated by their high PVN Crf mRNA expression; the blunted activity of HPT axis, by the decreased hypophysiotropic PVN Trh mRNA expression. Trh impaired expression to the positive energy balance in LPF, accounted for their ARC leptin resistance, evinced by an increased Npy and Socs3 mRNA expression. We concluded that the hyperphagia of prepuberal LPF animals could account for the HPA axis hyperactivity and for the HPT blocked function due to the altered ARC leptin signaling and impaired NPY regulation on PVN TRH neurons.

Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus–pituitary–thyroid axis (HPT) is reduced, whereas that of the hypothalamus–pituitary–adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2–3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.