SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet

Sci Rep. 2017 Aug 21;7(1):8982. doi: 10.1038/s41598-017-08694-4.

Abstract

Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5'-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / analysis
  • Animals
  • Diet, High-Fat*
  • Disease Models, Animal
  • Female
  • Forkhead Box Protein O3 / analysis
  • Intra-Abdominal Fat / pathology*
  • Kidney / pathology*
  • Male
  • Obesity / pathology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / analysis
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Sex Factors
  • Sirtuin 1 / analysis*
  • Stress, Physiological*

Substances

  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • AMP-Activated Protein Kinases
  • Sirtuin 1