Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat

Asokan Devarajan, Rajasekaran Namakkal Soorappan, Claire Valburg, Ekambaram Ganapathy, Snehal Bindra, William A. Freije

Research output: Contribution to journalArticle

Abstract

Intrauterine growth restriction (IUGR) leads to adult obesity, cardiovascular disease, and non-alcoholic fatty liver disease/steatohepatitis. Animal models have shown that combined intrauterine and early postnatal calorie restriction (IPCR) ameliorates these sequelae in adult life. The mechanism by which IPCR protects against adult onset disease is not understood. Autophagy, a lysosomal degradative process, recycles cellular constituents and eliminates damaged organelles, proteins, and oxidants. In this study, we hypothesized that IPCR could regulate autophagy in the liver of male rat offspring. At birth (d1) of male IUGR rat offspring and on day 21 (p21) of life, IPCR male rat offspring had a profound decrease in hepatic autophagy in all three stages of development: initiation, elongation, and maturation. However, upon receiving a normal diet ad-lib throughout adulthood, aged IPCR rats (day 450 of life (p450)), had increased hepatic autophagy, in direct contrast to what was seen in early life. The decreased autophagy at d21 led to the accumulation of ubiquitinated proteins and lipid oxidative products, whereas the increased autophagy in late life had the opposite effect. Oxidized lipids were unchanged at d1 by IUGR treatment indicating that decreased autophagy precedes oxidative stress in early life. When cellular signaling pathways regulating autophagy were examined, the 5′ adenosine monophosphate-activated protein kinase pathway (AMPK), and not endoplasmic stress pathways, was found to be altered, suggesting that autophagy is regulated through AMPK signaling pathway in IPCR rats. Taken together, this study reveals that the perinatal nutritional status establishes a nutritionally sensitive memory that enhances hepatic autophagy in late life, a process that perhaps acts as a protective mechanism to limited nutrition.

LanguageEnglish (US)
Pages592-600
Number of pages9
JournalFree Radical Biology and Medicine
Volume130
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Oxidative stress
Glucosephosphate Dehydrogenase
Autophagy
Oxidation-Reduction
Glutathione
Rats
Oxidative Stress
Mothers
Liver
Adenosine Monophosphate
Nutrition
Protein Kinases
Ubiquitinated Proteins
Cell signaling
Lipids
Oxidants
Elongation
Animals
Growth

Keywords

  • AMP activated protein kinase
  • Autophagy
  • Autophagy
  • Glucose-6-phosphate dehydrogenase
  • Glutathione
  • Intrauterine and postnatal calorie restriction
  • Intrauterine growth restriction
  • Oxidative stress
  • Perinatal calorie restriction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat. / Devarajan, Asokan; Soorappan, Rajasekaran Namakkal; Valburg, Claire; Ganapathy, Ekambaram; Bindra, Snehal; Freije, William A.

In: Free Radical Biology and Medicine, Vol. 130, 01.01.2019, p. 592-600.

Research output: Contribution to journalArticle

Devarajan, Asokan ; Soorappan, Rajasekaran Namakkal ; Valburg, Claire ; Ganapathy, Ekambaram ; Bindra, Snehal ; Freije, William A. / Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat. In: Free Radical Biology and Medicine. 2019 ; Vol. 130. pp. 592-600.
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