TY - JOUR

T1 - High-fat feeding increases hepatic vitamin C synthesis and its circulatory mobilization in mice

AU - Christensen, Britt Tranberg

AU - Hansen, Axel Jacob Kornerup

AU - Lykkesfeldt, Jens

PY - 2014

Y1 - 2014

N2 - PURPOSE: Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice-independent of dietary vitC-are able to modulate their vitC homeostasis during high-fat (HF) feeding.METHODS: Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates.RESULTS: HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P < 0.05). Hepatic de novo biosynthesis of vitC was upregulated (P < 0.05) as measured by GLO capacity, and liver vitC was reduced (P < 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT (P < 0.05).CONCLUSION: Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.

AB - PURPOSE: Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice-independent of dietary vitC-are able to modulate their vitC homeostasis during high-fat (HF) feeding.METHODS: Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates.RESULTS: HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P < 0.05). Hepatic de novo biosynthesis of vitC was upregulated (P < 0.05) as measured by GLO capacity, and liver vitC was reduced (P < 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT (P < 0.05).CONCLUSION: Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.

U2 - 10.1007/s00394-014-0694-z

DO - 10.1007/s00394-014-0694-z

M3 - Journal article

C2 - 24700376

VL - 53

SP - 1441

EP - 1444

JO - European Journal of Nutrition

JF - European Journal of Nutrition

SN - 1436-6207

IS - 6

ER -