Oral Presentation Australian & New Zealand Obesity Society 2015 Annual Scientific Meeting

Investigating the impact of Vitamin C on adiponectin secretion and metabolic parameters in a mouse model of Vitamin C deficiency (#14)

Johanna L Barclay 1 , Choaping Ng 1 , Sahar Keshvari 1 , Jonathan P Whitehead 1
  1. Metabolic Medicine, Mater Research Institute, University of Queensland, Brisbane, QLD, Australia

Compelling epidemiological data suggests that low Vitamin C levels are associated with obesity and obesity-related disease such as type 2 diabetes and cardiovascular disease; however numerous supplementation studies have failed to demonstrate benefits.  The basis for this disparity is unknown, but failure to identify Vitamin C-deficient subjects (approximately 10-20% in Western populations), and the heterogeneity in Vitamin C metabolism between individuals, may significantly contribute.  We previously reported that human adipocytes supplemented with Vitamin C in vitro, exhibited a dose-dependent increase in secretion of the most metabolically active (high molecular weight - HMW) form of the anti-diabetic, cardioprotective hormone adiponectin but not total adiponectin1.

We have now extended these observations in a pre-clinical model of Vitamin C deficiency, the Gulo-/- mouse.  Like humans, the key gene in the biosynthetic pathway of Vitamin C (L-gulonolactone oxidase) is defective in Gulo-/- mice making them dependent on dietary intake.  We found Gulo-/- mice supplemented with low Vitamin C (330 mg/ml  - a ‘maintenance dose’ to prevent scurvy but not render mice replete) had lower levels of HMW adiponectin than WT littermates, and supplementation with high Vitamin C (3300 mg/ml) for 3 weeks significantly increased HMW adiponectin 2-fold.  Circulating levels of HMW adiponectin returned to baseline 1 week after a reversal to low Vitamin C supplementation.  In contrast, total adiponectin was not different between WT and Gulo-/- mice, nor was it affected by Vitamin C supplementation.

These results fully recapitulate our in vitro findings1 as well as clinical trials which have found no correlation between Vitamin C and total adiponectin, and provide a foundation for further preclinical investigation into the impact of Vitamin C on adiponectin and cardiometabolic parameters.  We anticipate these results will provide the basis for rational investigations in humans.

  1. Rose, F. J. et al. Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes. Diabetes Obes Metab 12, 1084-1089, (2010).