Macronutrients Differentially Regulate PFKFB3 Expression and Increase Inflammation in Intestinal Epithelial Cells Conference Paper uri icon

abstract

  • The gene PFKFB3 encodes for inducible 6phosphofructo2kinase, an important regulatory enzyme of glycolysis that is increased in small intestine (SI) in response to highfat diet (HFD) feeding. However, it is unclear how macronutrients individually regulate PFKFB3 in small intestinal epithelial cells (IEC), the primary site of nutrient absorption and nutrient hostcell interactions. Also, how the inflammatory status of IECs changes in response to different macronutrients and altered PFKFB3 is unknown. The aim of this study was to investigate nutrient regulation of PFKFB3 and inflammatory cytokines in IECs isolated from SI. Male C57BL/6J mice were fed a lowfat diet (LFD) or HFD for 12 weeks and at harvest the SI was removed and IECs isolated and preserved. Also, CMT93, the mouse intestinederived cell line, was used to determine which macronutrients differentially regulate PFKFB3 and inflammatory cytokines. Cells were grown in low glucose (LG) or high glucose (HG) medium and treated with bovine serum albumin (BSA; control) or palmitate for 4 or 24 hrs. Analyses of primary IECs showed decreased PFKFB3 and increased inflammatory cytokines in HFD vs LFDfed animals. In addition, both PFKFB3 and inflammatory cytokines were increased in cells grown in HG+BSA for 24 hours, as compared to LG+BSA. Interestingly, PFKFB3 was decreased and inflammatory cytokines increased in response to 24 hours of palmitate, regardless of glucose concentration. These findings indicate that PFKFB3 and the inflammatory response in IECs seem to be differentially regulated by carbohydrates and fatty acids. Specifically, saturated fatty acids reduce PFKFB3 amount and contribute to intestinal inflammation. This study was funded by NIH.

published proceedings

  • FASEB JOURNAL

author list (cited authors)

  • Botchlett, R., Hu, X., Qi, T., Zhao, J., Li, H., & Wu, C.

citation count

  • 0

complete list of authors

  • Botchlett, Rachel||Hu, Xiang||Qi, Ting||Zhao, JiaJia||Li, Honggui||Wu, Chaodong

publication date

  • April 2015

publisher