Continued Postnatal Administration of Resveratrol Prevents Diet-Induced Metabolic Syndrome in Rat Offspring Born Growth Restricted
- Vernon W. Dolinsky1,2,3,4,5,
- Christian F. Rueda-Clausen2,3,4,5,6,
- Jude S. Morton2,3,5,7,
- Sandra T. Davidge2,3,4,5,6,7 and
- Jason R.B. Dyck1,2,3,4,5⇓
- 1Department of Pediatrics, University of Alberta, Edmonton, Canada
- 2Women and Children’s Health Research Institute, University of Alberta, Edmonton, Canada
- 3Cardiovascular Research Centre, University of Alberta, Edmonton, Canada
- 4Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
- 5Alberta Diabetes Institute, University of Alberta, Edmonton, Canada
- 6Department of Physiology, University of Alberta, Edmonton, Canada
- 7Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada
- Corresponding author: Jason R.B. Dyck, .
V.W.D. and C.F.R.-C. contributed equally to this study.
OBJECTIVE A prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) increases the susceptibility to develop metabolic syndrome (MetS) later in life. Since resveratrol (Resv), the polyphenol produced by plants, exerts insulin-sensitizing effects, we tested whether Resv could prevent deleterious metabolic effects of being born IUGR.
RESEARCH DESIGN AND METHODS Pregnant rats were exposed to either a normoxic (control; 21% O2) or a hypoxic (IUGR; 11.5% O2) environment during the last third of gestation. After weaning, male offspring were randomly assigned to receive either a high-fat (HF; 45% fat) diet or an HF diet with Resv (4 g/kg diet) for 9 weeks when various parameters of the MetS were measured.
RESULTS Relative to normoxic controls, hypoxia-induced IUGR offspring developed a more severe MetS, including glucose intolerance and insulin resistance, increased intra-abdominal fat deposition and intra-abdominal adipocyte size, and increased plasma triacylglycerol (TG) and free fatty acids, as well as peripheral accumulation of TG, diacylglycerol, and ceramides. In only IUGR offspring, the administration of Resv reduced intra-abdominal fat deposition to levels comparable with controls, improved the plasma lipid profile, and reduced accumulation of TG and ceramides in the tissues. Moreover, Resv ameliorated insulin resistance and glucose intolerance as well as impaired Akt signaling in the liver and skeletal muscle of IUGR offspring and activated AMP-activated protein kinase, which likely contributed to improved metabolic parameters in Resv-treated IUGR rats.
CONCLUSIONS Our results suggest that early, postnatal administration of Resv can improve the metabolic profile of HF-fed offspring born from pregnancies complicated by IUGR.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0374/-/DC1.
V.W.D. is currently affiliated with the Department of Pharmacology, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
- Received March 18, 2011.
- Accepted June 28, 2011.
- © 2011 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.