Role of neonatal hyperleptinaemia on serum adiponectin and suppressor of cytokine signalling-3 expression in young rats

Abstract

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 mg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (þ42·5 %) and lower levels of serum adiponectin (243·2 %). The hypothalamic expression of OB-Rb was lower (2 22 %) and SOCS-3 was higher (þ52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats

“…This result could explain the hyperphagia observed in adult overfed animals. In other models of programming during lactation, our group showed that leptin injections on the first 10 days of life program for hyperleptinemia when they were 30 days old, lower Ob-Rb and higher SOCS3 content in hypothalamus [63], similar to our present results for adult SL rats. As stated before, SOCS3 does an intracellular feedback regulation on leptin signaling pathway; blocking JAK2 phosphorylation and increase in hypothalamic SOCS3 expression have been clearly related with leptin resistance in obesity [64][65][66][67].…”

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

“…Using the same experimental model of programming, Dutra et al (18) demonstrated lower expression of OBR in hypothalamus and thyroid in leptin of 30-day-old leptin-programmed rats. In the present study, a very similar profile was found with lower expression of OBR in medulla, suggesting leptin resistance also in the periphery, similar to what we have found in the hypothalamus (38,53). It is well known that hyperleptinemia causes downregulation on OBRs, especially in the hypothalamus.…”

Flaxseed supplementation of rats during lactation changes the adiposity and glucose homeostasis of their offspring

“…However, different from the programming effect of hyperleptinemia during lactation (Toste et al 2006a) that was associated with hyperleptinemia and leptin resistance at adulthood, we did not find a programming effect of maternal flaxseed diet during lactation. On the other hand, neonatal leptin programming is also associated with hyperinsulinemia and hypoadiponectinemia in the adult offspring (Passos et al 2009). In this recent paper, we showed that SOCS3 (suppressor of cytokine signalling-3) may play a role in this leptin and insulin resistance.…”