Grape Pomace and Resveratrol Do Not Restore Glucose Tolerance in the Ovariectomized Rat
Authors: Anderson Eoin , Dyck David J 
Published: November 2023

ObjectiveThe loss of estrogen in females is associated with a worsening of insulin sensitivity. Natural compounds such as resveratrol (RESV) have potential insulin sensitizing effects. Grape pomace (GP) is a byproduct of winemaking, and contains RESV and other antioxidants. To our knowledge, the efficacy of RESV and GP in restoring glucose tolerance in ovariectomized (OVX) rats has not been explored.MethodsPhyto‐estrogen free diet was administered ad libitum to sham control (SHAM, n=10) and OVX (n=40) female Sprague‐Dawley rats for 12 wks until the onset of glucose intolerance in OVX rats. Glucose tolerance was assessed with an intraperitoneal glucose tolerance test (IPGTT; 0.5g glucose/kg body mass) over a 2 hr period. Following the induction of glucose intolerance, OVX animals were divided into treatment and control groups (n=10 each). The first treatment group received a daily physiological dose of estrogen (E2, 28μg/kg body mass) orally via a Nutella cream (5μL sesame oil/1g Nutella/kg body mass). Another group of rats received a daily dose of RESV (5mg/kg body mass) mixed into the Nutella cream. Finally, the last treatment group had GP supplemented at 1.5% of their diet which provides about 5mg/kg body mass of RESV per day. SHAM, OVX CON, and OVX GP each received a daily dose of untreated Nutella. Animals were allowed ad libitum access to food, and treatment continued for 6 wks. At the end of the treatment period, IPGTTs were performed as well as an intraperitoneal insulin tolerance test (IPTT). 2–3 d after the TTs, terminal surgeries were performed during which muscle red (RG) and white gastrocnemius (WG) muscles and subcutaneous and visceral adipose tissue was harvested before and 10 min after insulin injection (1 μg/kg body mass). Liver was sampled post insulin injection. All tissues were stored at −80°C. Tissues were analyzed for insulin signaling (phospho‐AktSer473). Visceral adipose was preserved and stained for analysis of adipocyte size.ResultsOVX animals were significantly heavier than control animals at the onset of glucose intolerance and this did not change throughout the treatment period. OVX animals consumed significantly more food during the first 6 wks following ovariectomy. OVX rats were glucose intolerant compared to SHAM controls after 12 wks (area under the curve (AUC): SHAM=316 vs OVX=CON 506 mM × min, p=0.0002,); none of the treatments restored normal glucose tolerance during the subsequent 6 wks (AUC OVX CON=452, E2=493, RESV=404, GP=453 vs SHAM=223 mM × min, p=.0121). Insulin tolerance was not worsened in OVX rats, and was unaffected with treatment. No difference in liver pAkt content was found between SHAM and OVX animals (p=0.3599). A significant increase was detected in pAkt in insulin simulated RG muscle compared to basal (p<0.0001); however there was no effect of ovariectomy (p=0.3680), and the interaction was not significant (p=0.3660). Similarly, pAkt content was increased in insulin stimulated WG muscle (p<0.0001), but there was no effect of ovariectomy (p=0.7822) or interaction (p=0.8037). Adipocyte size was significantly increased in the E2 (p=0.0552) and RESV (p=0.0121) groups compared to SHAM.ConclusionRESV and GP were not effective in restoring normal glucose tolerance in OVX rats.Support or Funding InformationOntario Ministry of Agriculture, Food, and Rural AffairsNatural Sciences and Engineering Research Council of Canada