Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response

Xin Guo, Honggui Li, Hang Xu, Vera Halim, Laura N. Thomas, Shih Lung Woo, Yuqing Huo, Y. Eugene Chen, Joseph M. Sturino, Chaodong Wu

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalJournal of Nutritional Biochemistry
Volume24
Issue number5
DOIs
StatePublished - May 1 2013

Fingerprint

Phosphofructokinase-2
PPAR gamma
Nutrition
Intestines
Chemical activation
Diet
Fats
High Fat Diet
rosiglitazone
Overnutrition
Insulin
Mitogen-Activated Protein Kinase 8
Insulin Resistance
Toll-Like Receptor 4
Phosphorylation
NF-kappa B
Hypoglycemic Agents
Fat-Restricted Diet
Glycolysis
Genes

Keywords

  • Inducible 6-phosphofructo-2-kinase
  • Inflammatory response
  • Intestine
  • Overnutrition
  • PPARγ

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response. / Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Thomas, Laura N.; Woo, Shih Lung; Huo, Yuqing; Chen, Y. Eugene; Sturino, Joseph M.; Wu, Chaodong.

In: Journal of Nutritional Biochemistry, Vol. 24, No. 5, 01.05.2013, p. 770-775.

Research output: Contribution to journalArticle

Guo, Xin ; Li, Honggui ; Xu, Hang ; Halim, Vera ; Thomas, Laura N. ; Woo, Shih Lung ; Huo, Yuqing ; Chen, Y. Eugene ; Sturino, Joseph M. ; Wu, Chaodong. / Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response. In: Journal of Nutritional Biochemistry. 2013 ; Vol. 24, No. 5. pp. 770-775.
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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.",
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AU - Xu, Hang

AU - Halim, Vera

AU - Thomas, Laura N.

AU - Woo, Shih Lung

AU - Huo, Yuqing

AU - Chen, Y. Eugene

AU - Sturino, Joseph M.

AU - Wu, Chaodong

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AB - 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.

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