Differential effects of acute versus chronic dietary fructose consumption on metabolic responses in FVB/N mice

Am J Physiol Regul Integr Comp Physiol. 2022 Aug 1;323(2):R255-R266. doi: 10.1152/ajpregu.00174.2021. Epub 2022 May 17.


Increased human consumption of high-fructose corn syrup has been linked to the marked increase in obesity and metabolic syndrome. Previous studies on the rapid effects of a high-fructose diet in mice have largely been confined to the C57BL/6 strains. In the current study, the FVB/N strain of mice that are resistant to diet-induced weight gain were used and fed a control or high-fructose diet for 48 h or for 12 wk. Many of the previously reported changes that occurred upon high-fructose feeding for 48 h in C57BL/6 mice were recapitulated in the FVB/N mice. However, the acute increases in fructolytic and lipogenic gene expression were completely lost during the 12-wk dietary intervention protocol. Furthermore, there was no significant weight gain in FVB/N mice fed a high-fructose diet for 12 wk, despite an overall increase in caloric consumption and an increase in average epididymal adipocyte cell size. These findings may be in part explained by a commensurate increase in energy expenditure and in carbohydrate utilization in high-fructose-fed animals. Overall, these findings demonstrate that FVB/N mice are a suitable model for the study of the effects of dietary intervention on metabolic and molecular parameters. Furthermore, the rapid changes in hepatic gene expression that have been widely reported were not sustained over a longer time course. Compensatory changes in energy expenditure and utilization may be in part responsible for the differences obtained between acute and chronic high-fructose feeding protocols.

Keywords: adipose tissue secretome; energy expenditure; hepatic gene expression; high-fructose corn syrup.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Diet*
  • Fructose* / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Weight Gain


  • Fructose