Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response

Yuqing Huo, Xin Guo, Honggui Li, Huan Wang, Weiyu Zhang, Ying Wang, Huaijun Zhou, Zhanguo Gao, Sucheta Telang, Jason Chesney, Y. Eugene Chen, Jianping Ye, Robert S. Chapkin, Chaodong Wu

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Adiposity is commonly associated with adipose tissue dysfunction and many overnutrition-related metabolic diseases including type 2 diabetes. Much attention has been paid to reducing adiposity as a way to improve adipose tissue function and systemic insulin sensitivity. PFKFB3/iPFK2 is a master regulator of adipocyte nutrient metabolism. Using PFKFB3+/- mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity and systemic insulin resistance. On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. This was attributed to a smaller increase in adiposity in PFKFB3+/- mice than in wild-type controls. However, HFD-induced systemic insulin resistance was more severe in PFKFB3+/- mice than in wild-type littermates. Compared with wild-type littermates, PFKFB3+/- mice exhibited increased severity of HFD-induced adipose tissue dysfunction, as evidenced by increased adipose tissue lipolysis, inappropriate adipokine expression, and decreased insulin signaling, as well as increased levels of proinflammatory cytokines in both isolated adipose tissue macrophages and adipocytes. In an in vitro system, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes caused a decrease in the rate of glucose incorporation into lipid but an increase in the production of reactive oxygen species. Furthermore, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes inappropriately altered the expression of adipokines, decreased insulin signaling, increased the phosphorylation states of JNK and NFβB p65, and enhanced the production of proinflammatory cytokines. Together, these data suggest that PFKFB3/iPFK2, although contributing to adiposity, protects against diet-induced insulin resistance and adipose tissue inflammatory response.

Original languageEnglish (US)
Pages (from-to)3713-3721
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number6
DOIs
StatePublished - Feb 5 2010

Fingerprint

Phosphofructokinase-2
Adiposity
Nutrition
Insulin Resistance
Adipose Tissue
Insulin
Tissue
Diet
Adipocytes
High Fat Diet
Adipokines
Fats
Overnutrition
Cytokines
Phosphorylation
Macrophages
Lipolysis
Metabolic Diseases
Medical problems
Metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response. / Huo, Yuqing; Guo, Xin; Li, Honggui; Wang, Huan; Zhang, Weiyu; Wang, Ying; Zhou, Huaijun; Gao, Zhanguo; Telang, Sucheta; Chesney, Jason; Chen, Y. Eugene; Ye, Jianping; Chapkin, Robert S.; Wu, Chaodong.

In: Journal of Biological Chemistry, Vol. 285, No. 6, 05.02.2010, p. 3713-3721.

Research output: Contribution to journalArticle

Huo, Y, Guo, X, Li, H, Wang, H, Zhang, W, Wang, Y, Zhou, H, Gao, Z, Telang, S, Chesney, J, Chen, YE, Ye, J, Chapkin, RS & Wu, C 2010, 'Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response', Journal of Biological Chemistry, vol. 285, no. 6, pp. 3713-3721. https://doi.org/10.1074/jbc.M109.058446
Huo, Yuqing ; Guo, Xin ; Li, Honggui ; Wang, Huan ; Zhang, Weiyu ; Wang, Ying ; Zhou, Huaijun ; Gao, Zhanguo ; Telang, Sucheta ; Chesney, Jason ; Chen, Y. Eugene ; Ye, Jianping ; Chapkin, Robert S. ; Wu, Chaodong. / Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 6. pp. 3713-3721.
@article{8f0468e25b2d4ea8ad9a03855534ab25,
title = "Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response",
abstract = "Adiposity is commonly associated with adipose tissue dysfunction and many overnutrition-related metabolic diseases including type 2 diabetes. Much attention has been paid to reducing adiposity as a way to improve adipose tissue function and systemic insulin sensitivity. PFKFB3/iPFK2 is a master regulator of adipocyte nutrient metabolism. Using PFKFB3+/- mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity and systemic insulin resistance. On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. This was attributed to a smaller increase in adiposity in PFKFB3+/- mice than in wild-type controls. However, HFD-induced systemic insulin resistance was more severe in PFKFB3+/- mice than in wild-type littermates. Compared with wild-type littermates, PFKFB3+/- mice exhibited increased severity of HFD-induced adipose tissue dysfunction, as evidenced by increased adipose tissue lipolysis, inappropriate adipokine expression, and decreased insulin signaling, as well as increased levels of proinflammatory cytokines in both isolated adipose tissue macrophages and adipocytes. In an in vitro system, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes caused a decrease in the rate of glucose incorporation into lipid but an increase in the production of reactive oxygen species. Furthermore, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes inappropriately altered the expression of adipokines, decreased insulin signaling, increased the phosphorylation states of JNK and NFβB p65, and enhanced the production of proinflammatory cytokines. Together, these data suggest that PFKFB3/iPFK2, although contributing to adiposity, protects against diet-induced insulin resistance and adipose tissue inflammatory response.",
author = "Yuqing Huo and Xin Guo and Honggui Li and Huan Wang and Weiyu Zhang and Ying Wang and Huaijun Zhou and Zhanguo Gao and Sucheta Telang and Jason Chesney and Chen, {Y. Eugene} and Jianping Ye and Chapkin, {Robert S.} and Chaodong Wu",
year = "2010",
month = "2",
day = "5",
doi = "10.1074/jbc.M109.058446",
language = "English (US)",
volume = "285",
pages = "3713--3721",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "6",

}

TY - JOUR

T1 - Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response

AU - Huo, Yuqing

AU - Guo, Xin

AU - Li, Honggui

AU - Wang, Huan

AU - Zhang, Weiyu

AU - Wang, Ying

AU - Zhou, Huaijun

AU - Gao, Zhanguo

AU - Telang, Sucheta

AU - Chesney, Jason

AU - Chen, Y. Eugene

AU - Ye, Jianping

AU - Chapkin, Robert S.

AU - Wu, Chaodong

PY - 2010/2/5

Y1 - 2010/2/5

N2 - Adiposity is commonly associated with adipose tissue dysfunction and many overnutrition-related metabolic diseases including type 2 diabetes. Much attention has been paid to reducing adiposity as a way to improve adipose tissue function and systemic insulin sensitivity. PFKFB3/iPFK2 is a master regulator of adipocyte nutrient metabolism. Using PFKFB3+/- mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity and systemic insulin resistance. On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. This was attributed to a smaller increase in adiposity in PFKFB3+/- mice than in wild-type controls. However, HFD-induced systemic insulin resistance was more severe in PFKFB3+/- mice than in wild-type littermates. Compared with wild-type littermates, PFKFB3+/- mice exhibited increased severity of HFD-induced adipose tissue dysfunction, as evidenced by increased adipose tissue lipolysis, inappropriate adipokine expression, and decreased insulin signaling, as well as increased levels of proinflammatory cytokines in both isolated adipose tissue macrophages and adipocytes. In an in vitro system, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes caused a decrease in the rate of glucose incorporation into lipid but an increase in the production of reactive oxygen species. Furthermore, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes inappropriately altered the expression of adipokines, decreased insulin signaling, increased the phosphorylation states of JNK and NFβB p65, and enhanced the production of proinflammatory cytokines. Together, these data suggest that PFKFB3/iPFK2, although contributing to adiposity, protects against diet-induced insulin resistance and adipose tissue inflammatory response.

AB - Adiposity is commonly associated with adipose tissue dysfunction and many overnutrition-related metabolic diseases including type 2 diabetes. Much attention has been paid to reducing adiposity as a way to improve adipose tissue function and systemic insulin sensitivity. PFKFB3/iPFK2 is a master regulator of adipocyte nutrient metabolism. Using PFKFB3+/- mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity and systemic insulin resistance. On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. This was attributed to a smaller increase in adiposity in PFKFB3+/- mice than in wild-type controls. However, HFD-induced systemic insulin resistance was more severe in PFKFB3+/- mice than in wild-type littermates. Compared with wild-type littermates, PFKFB3+/- mice exhibited increased severity of HFD-induced adipose tissue dysfunction, as evidenced by increased adipose tissue lipolysis, inappropriate adipokine expression, and decreased insulin signaling, as well as increased levels of proinflammatory cytokines in both isolated adipose tissue macrophages and adipocytes. In an in vitro system, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes caused a decrease in the rate of glucose incorporation into lipid but an increase in the production of reactive oxygen species. Furthermore, knockdown of PFKFB3/iPFK2 in 3T3-L1 adipocytes inappropriately altered the expression of adipokines, decreased insulin signaling, increased the phosphorylation states of JNK and NFβB p65, and enhanced the production of proinflammatory cytokines. Together, these data suggest that PFKFB3/iPFK2, although contributing to adiposity, protects against diet-induced insulin resistance and adipose tissue inflammatory response.

UR - http://www.scopus.com/inward/record.url?scp=77950484849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950484849&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.058446

DO - 10.1074/jbc.M109.058446

M3 - Article

VL - 285

SP - 3713

EP - 3721

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 6

ER -