Glucocorticoids contribute to metabolic and liver impairments induced by lactation overnutrition in male adult rats

Frontiers in Physiology

Physiology

Dimas A. M. Zaia¹  Gabriela Mendicelli Lopes²  Flaviane de Fatima Silva³  Fabio Bessa Lima³  Ayumi Cristina Medeiros Komino³  Andressa B. Martins⁴  Camila F. de Souza⁴  Cassia Thaïs B. V. Zaia⁵  Ernane Torres Uchoa⁵  Ana Luiza M. Wunderlich⁶  Larissa Rugila S. Stopa⁶ 

[1] Department of Chemistry, State University of Londrina, Londrina, Brazil;Department of Physiological Sciences, State University of Londrina, Londrina, Brazil;Department of Physiology and Biophysics, University of Sao Paulo, Sao Paulo, Brazil;Multicenter Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil;Multicenter Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil;Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil;Department of Physiological Sciences, State University of Londrina, Londrina, Brazil;Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil;

关键词: adrenalectomy;    corticosterone;    litter size reduction;    triglycerides;    obesity;   

DOI  :  10.3389/fphys.2023.1161582

 received in 2023-02-08, accepted in 2023-04-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Lactation overnutrition is a programming agent of energy metabolism, and litter size reduction leads to the early development of obesity, which persists until adulthood. Liver metabolism is disrupted by obesity, and increased levels of circulating glucocorticoids are pointed as a possible mediator for the obesity development, since bilateral adrenalectomy (ADX) can reduce obesity in different models of obesity.Methods: This study aimed to evaluate the effects of glucocorticoids on metabolic changes and liver lipogenesis and insulin pathway induced by lactation overnutrition. For this, on the postnatal day 3 (PND), 3 pups (small litter—SL) or 10 pups (normal litter—NL) were kept with each dam. On PND 60, male Wistar rats underwent bilateral adrenalectomy (ADX) or fictitious surgery (sham), and half of ADX animals received corticosterone (CORT- 25 mg/L) diluted in the drinking fluid. On PND 74, the animals were euthanized by decapitation for trunk blood collection, and liver dissection and storage.Results and Discussion: SL rats presented increased corticosterone, free fatty acids, total and LDL-cholesterol plasma levels, without changes in triglycerides (TG) and HDL-cholesterol. The SL group also showed increased content of liver TG, and expression of fatty acid synthase (FASN), but decreased expression of PI3Kp110 in the liver, compared to NL rats. In the SL group, the ADX decreased plasma levels of corticosterone, FFA, TG and HDL cholesterol, liver TG, and liver expression of FASN, and IRS2, compared to sham animals. In SL animals, CORT treatment increased plasma levels of TG and HDL cholesterol, liver TG, and expression of FASN, IRS1, and IRS2, compared with the ADX group. In summary, the ADX attenuated plasma and liver changes observed after lactation overnutrition, and CORT treatment could reverse most ADX-induced effects. Thus, increased circulating glucocorticoids are likely to play a pivotal role in liver and plasma impairments induced by lactation overnutrition in male rats.

【 授权许可】

Unknown   
Copyright © 2023 de Souza, Stopa, Martins, Wunderlich, Lopes, de Fatima Silva, Komino, Zaia, Zaia, Lima and Uchoa.