Grape seed procyanidins administered at physiological doses to rats during pregnancy and lactation promote lipid oxidation and up-regulate AMPK in the muscle of male offspring in adulthood

J Nutr Biochem. 2015 Sep;26(9):912-20. doi: 10.1016/j.jnutbio.2015.03.003. Epub 2015 Apr 15.


The aim of the present study was to test whether the administration of a grape seed procyanidin extract (GSPE) during pregnancy and lactation, at doses extrapolated to human consumption, programs male offspring toward improved metabolism in adulthood. For this purpose, female rats were fed a normal-fat diet (NFD) and treated with either GSPE (25 mg kg(-1) of body weight/day) or vehicle during gestation and lactation. The metabolic programming effects of GSPE were evaluated in the male offspring fed NFD from 30 to 170 days of life. No changes were observed in body weight, adiposity, circulating lipid profile and insulin sensitivity between the offspring of dams treated with GSPE (STD-GSPE group) and their counterparts (STD-veh). However, the STD-GSPE offspring had lower circulating levels of C-reactive protein and lower respiratory quotient values, shifting whole-body energy catabolism from carbohydrate to fat oxidation. Furthermore, the STD-GSPE animals also exhibited increased levels of total and phosphorylated AMP-activated protein kinase (AMPK) and an over-expression of the mRNA levels of key genes related to fatty acid uptake (Fatp1 and CD36) and β-oxidation (pparα and had) in skeletal muscle. Our results indicate that GSPE programs healthy male offspring towards a better circulating inflammatory profile and greater lipid utilisation in adulthood. The metabolic programming effects of GSPE that are related to the enhancement of fatty acid oxidation in skeletal muscle seem to be mediated, at least in part, by AMPK. These findings could be of relevance in the prevention of pathologies associated to lifestyle and aging, such as obesity and insulin resistance.

Keywords: AMPK; Grape seed procyanidins; Inflammation; Lipid oxidation; Metabolic programming; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl-CoA Dehydrogenase / chemistry
  • 3-Hydroxyacyl-CoA Dehydrogenase / genetics
  • 3-Hydroxyacyl-CoA Dehydrogenase / metabolism
  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • CD36 Antigens / chemistry
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • Dietary Supplements*
  • Enzyme Induction
  • Fatty Acid-Binding Proteins / agonists
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism
  • Female
  • Fetal Development
  • Grape Seed Extract / administration & dosage*
  • Lactation / metabolism*
  • Lipid Metabolism*
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • PPAR alpha / agonists
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Phosphorylation
  • Pregnancy
  • Proanthocyanidins / administration & dosage*
  • Protein Processing, Post-Translational
  • Rats


  • CD36 Antigens
  • Cd36 protein, rat
  • Fatty Acid-Binding Proteins
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • PPAR alpha
  • Proanthocyanidins
  • Slc27a1 protein, rat
  • 3-Hydroxyacyl-CoA Dehydrogenase
  • AMP-Activated Protein Kinases