Hepatic Autophagy Gene Expression Is Induced by Post‐Weaning Diets in Sprague‐Dawley Rats fed with A Low‐Protein Diet During Lactation

Abstract

BackgroundBoth maternal dietary protein restriction and excess fat intake are associated with numerous metabolic responses including the activation of transcription factor 4 (ATF4). ATF4 is one of the master regulators of stress response pathways, which potentially program autophagy genes expression in the liver of offspring rats.HypothesisThe current study tested the hypothesis that lactational low‐protein (LP) diet and postnatal high‐fat (HF) diet induce a metabolic mismatch that activates autophagy gene expression through the activation of ATF4 in the liver of offspring rats.MethodsTimed‐pregnant Sprague‐Dawley rats were fed a control diet (C, 20% protein) during gestation followed by either a LP diet (8% protein) or the control diet during lactation for 21 days. At weaning, the offspring was fed either C (16% fat) or HF (45% fat) to generate three offspring groups: C/C/C, C/LP/C and C/LP/HF. At 12 weeks of age, liver samples of male and female rats were collected for analysis.ResultsLactational LP diet and post‐weaning HF diet induce autophagy gene expression differentially in the liver of male and female offspring. mRNA expression of Beclin1, p62/sqstm1, LC3b and Atg5, crucial markers of autophagy, was significantly upregulated by lactational LP diet (C/LP/C when compared to C/C/C, p<0.05) in female offspring, but not in male offspring. Consistent with that, mRNA expression of other autophagy related genes including Atg16l1, Atg12 Atg3, Gabarapl2, Atg7, Atg10 and Gabarap increased significantly in the female offspring only. Moreover, autophagy genes Atg16l1, Atg12, Atg3, Beclin1, p62/sqstm1, LC3b, Gabarapl2, Atg7, Atg10, Gabarap, and Atg5 were expressed at a higher level by post‐weaning HF diet (C/LP/HF when compared to C/LP/C, p<0.05) in both male and female offspring. A master regulator of stress pathway, transcription factor ATF4, also displayed differential expression in the mismatched dietary groups.ConclusionLactational low‐protein diet induced autophagy related gene expression in female offspring and the induction was further augmented by a post‐weaning high‐fat diet. On the other hand, in the liver of male offspring, only post‐weaning high‐fat diet induced mRNA expression of autophagy related genes. The differential regulation of autophagy by diets, sex, and developmental periods could be explained by dysregulation of stress response pathway involving transcription factor ATF4. Overall, our data demonstrated that lactational low‐protein diet may impact autophagy pathway more in female offspring than in male offspring rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.