Comparison of tissue concentrations in male and female C57BL/6 mice in response to vitamin K manipulation (1041.4)

The tissue-specific response to dietary vitamin K (VK) manipulation has not been well studied in mice. This limits the use of genetically modified mouse models in VK studies. The objective of this study was to determine the sex-specific effects of dietary VK manipulation on serum, liver and extra-hepatic tissue VK concentrations in C57BL/6 mice (n=64). Mice were weight-matched and pair-fed a control diet (1.4±0.08 mg phylloquinone (PK) /kg) or VK-deficient diet (31±0.45 µg PK/kg) for 28 days. Liver, kidney, brain, pancreas, adipose tissue, and serum PK and menaquinone-4 (MK-4) concentrations were measured by HPLC. Data were log transformed and analyzed by a general linear model, stratified by diet. Male and female mice responded differently to dietary manipulation of VK in a tissue-dependent manner (for all sex by diet interactions p<0.031). Serum PK concentrations did not differ between males and females within each diet (p>0.95); no serum MK-4 was detected. Females on the control diet had significantly higher PK and MK-4 concentrations in adipose tissue, kidney, liver, pancreas, and brain compared to males (p<0.01). Only MK-4 concentrations in adipose tissue, liver, and pancreas did not differ between males and females on the deficient diet (p>0.44). Sex-specific differences in response to VK manipulation need to be considered when using animal models of VK metabolism. Grant Funding Source: Supported by the USDA/ARS Cooperative Agreement No. 58-1950-7-707