title: Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells.
abstract: The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 μmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients.
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Botchlett
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Honggui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Qi
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: JiaJia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Shih-Lung
authors.initials: SL
authors.lastname: Woo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Center for Animal Experiment, Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.|The Laboratory of Lipid &Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D059305:Diet, High-Fat; D004847:Epithelial Cells / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010168:Palmitates / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D015415:Biomarkers; D010168:Palmitates; C000595376:PFKFB3 protein, mouse; D025481:Phosphofructokinase-2; D005947:Glucose