title: Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response.
abstract: PFKFB3 is a target gene of peroxisome proliferator-activated receptor gamma (PPARγ) and encodes for inducible 6-phosphofructo-2-kinase (iPFK2). As a key regulatory enzyme that stimulates glycolysis, PFKFB3/iPFK2 links adipocyte metabolic and inflammatory responses. Additionally, PFKFB3/iPFK2 is involved in the effect of active PPARγ on suppressing overnutrition-induced adipose tissue inflammatory response, which accounts for the insulin-sensitizing and antidiabetic effects of PPARγ activation. Using PFKFB3/iPFK2-disrupted mice, the present study investigated the role of PFKFB3/iPFK2 in regulating overnutrition-associated intestine inflammatory response and in mediating the effects of PPARγ activation. In wild-type mice, intestine PFKFB3/iPFK2 was increased in response to high-fat diet (HFD) feeding compared with that in mice fed a low-fat diet. However, intestine PFKFB3/iPFK2 was decreased in PFKFB3/iPFK2-disrupted mice and did not respond to HFD feeding. Furthermore, on an HFD, PFKFB3/iPFK2-disrupted mice displayed a significant increase in major intestine proinflammatory indicators such as toll-like receptor 4 expression, c-Jun N-terminal kinase 1 and nuclear factor kappa B phosphorylation, and proinflammatory cytokine expression compared with wild-type littermates. Upon treatment with rosiglitazone, an agonist of PPARγ, intestine proinflammatory indicators were markedly decreased in wild-type mice, but to a much lesser degree in PFKFB3/iPFK2-disrupted mice. Overall, the status of HFD-induced intestine inflammatory response in all treated mice correlated inversely with systemic insulin sensitivity, indicated by the homeostasis model assessment of insulin resistance data. Together, these results suggest that PFKFB3/iPFK2 is critically involved in the effect of PPARγ activation on suppressing diet-induced intestine inflammatory response.
authors: Intercollegiate Faculty of Nutrition, Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors: Xin
authors: X
authors: Guo
authors: Honggui
authors: H
authors: Li
authors: Hang
authors: H
authors: Xu
authors: Vera
authors: V
authors: Halim
authors: Laura N
authors: LN
authors: Thomas
authors: Shih-Lung
authors: SL
authors: Woo
authors: Yuqing
authors: Y
authors: Huo
authors: Y Eugene
authors: YE
authors: Chen
authors: Joseph M
authors: JM
authors: Sturino
authors: Chaodong
authors: C
authors: Wu
mesh_terms: D017667:Adipocytes / Q000201:enzymology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001644:Bifidobacterium / Q000302:isolation & purification; D015153:Blotting, Western; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D006019:Glycolysis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D007422:Intestines / Q000201:enzymology* / Q000382:microbiology; D007778:Lactobacillus / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077154:Rosiglitazone; D025481:Phosphofructokinase-2; D048055:Mitogen-Activated Protein Kinase 8