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Developmental plasticity of endocrine disorders in obesity model primed by early weaning in dams
N S Lima1, E G Moura, J G Franco
1Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Insights
Early weaning in rats alters adipocyte development and thyroid function, leading to obesity-related metabolic changes in adulthood. This study highlights the long-term impact of early life stress on metabolic health.
Area of Science:
- Endocrinology
- Developmental Biology
- Metabolic Health
Background:
- Early weaning is a form of early-life stress impacting developmental plasticity.
- Adipose tissue morphology, adipokine expression, and endocrine function are sensitive to early-life conditions.
Purpose of the Study:
- To investigate the long-term effects of early weaning on adipocyte morphology, adipokine expression, and adrenal/thyroid function in rat offspring.
- To determine if early weaning primes offspring for metabolic disturbances in adulthood.
Main Methods:
- Rats were divided into early weaning (EW) and control groups.
- Adipocyte size, body fat mass, adipokine levels (leptin, adiponectin), and adrenal/thyroid hormones (T3, TSH, catecholamines, corticosterone) were measured at weaning (PN 21) and adulthood (PN 180).
Main Results:
- Neonatal EW pups showed reduced adipocyte size and body fat, with altered leptin expression and hypothyroidism (lower T3, TSH).
- Adult EW offspring exhibited increased food intake, body fat mass, adipocyte size, leptin, ADRβ3, and altered adiponectin levels.
- Adult EW rats had higher adrenal catecholamine content but normal corticosterone and thyroid status.
Conclusions:
- Early weaning induces hypothyroidism at weaning and adipocyte hypertrophy in adulthood, suggesting a link to obesity development.
- Changes in adrenal catecholamines and visceral adipocyte ADRβ3 in EW adults are indicative of metabolic dysfunction and increased cardiovascular risk.
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.
