Developmental Plasticity of Endocrine Disorders in Obesity Model Primed by Early Weaning in Dams

Abstract

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRβ3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition

“…This method programs for obesity, hyperleptinemia, leptin resistance (Bonomo et al 2007), and hypothyroidism (Bonomo et al 2008), and symptoms (including insulin resistance and an altered lipid profile) are similar to those of metabolic syndrome (Moura et al 2009). More recently, we obtained a similar profile in adult animals with a non-pharmacological model where a maternal bandage was used to cover the teats of the dam in the late lactation, thus also inducing an early weaning of offspring (Lima et al 2011(Lima et al , 2013.…”

Anti‐obesogenic effects of calcium prevent changes in the GLP‐1 profile in adult rats primed by early weaning

“…Treatment with GLP-1 or its analogue (liraglutide) induces adipogenesis via GLP1-R, both in vivo and in vitro, with higher adiponectin secretion and improvement in insulin sensitivity [29,32]. In fact, we observed that PN day 21 (PN21) EW rats had higher insulin sensitivity associated with lower adipocyte area [11,42]. In the present study, it is possible that high plasma GLP-1 content in EW pups promotes differentiation of preadipocytes, leading to a higher number of mature adipocytes that together with this initial higher insulin sensitivity contributes to obesity development in adulthood, when they have larger adipocytes and develop IR [42].…”

“…In adipose tissue, lower GLP1‐R expression was observed in the EW group at 180 days old, but was not observed in the EWCa group. Lower GLP‐1 receptor content in adipose tissue in EW offspring may contribute to the development of lower insulin sensitivity, which consistent with our previous findings that EW animals present IR . The normal GLP1‐R content in adipose tissue of EWCa animals indicates that calcium supplementation maintained the GLP‐1 response in this tissue and contributed to preventing the metabolic disorder that developed in EW animals.…”

“…Unfortunately, the basal metabolic rate and the locomotor activity of EW offspring were not evaluated, which is a limitation of our study. In previous studies, EW rats presented no change of serum thyroid hormones ; however, they showed a higher catecholamine content in adrenal tissue and higher ADRB3 expression in adipocytes, suggesting lower catecholamine secretion and action that contribute to lower energy expenditure.…”

“…The bandage procedure appeared not to generate significant stress in either dams or offspring. We measured the corticosteronemia of dams (data not shown) and offspring [42] and did not observe any changes in the EW group compared to the C group.…”