Disruption of endothelial Pfkfb3 ameliorates diet-induced murine insulin resistance

Qiuhua Yang, Jiean Xu, Qian Ma, Zhiping Liu, Yaqi Zhou, Yongfeng Cai, Xiaoxiao Mao, David Stepp, Neal Weintraub, David J. Fulton, Mei Hong, Yuqing Huo

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Overnutrition-induced endothelial inflammation plays a crucial role in high-fat diet (HFD)-induced insulin resistance in animals. Endothelial glycolysis plays a critical role in endothelial inflammation and proliferation, but its role in d iet-induced endothelial inflammation and subsequent insulin resistance has not been eluc idated. PFKFB3 is a critical glycolytic regulator, and its increased expression has been observed in adipose vascular endothelium of C57BL/6J mice fed with HFD in vivo, and in palmitate (PA)- treated primary human adipose microvascular endothelial cells (HAMECs) in vitro. We generated mice with Pfkfb3 deficiency selective for endothelial cells to examine the effect of endothelial Pfkfb3 in endothelial inflammation in metab olic organs and in the development of HFD-induced insulin resistance. EC Pfkfb3-deficient mice exhibited mitigated HFD-induced insulin resistance, including decreased body weight and fat mass, improved glucose clearance and insulin sensitivity, and alleviated adiposity and hepatic steatosis. Mechanistically, cultured PFKFB3 knockdown HAMECs showed decreased NF-?B activation induced by PA, and consequent suppressed adhesion mo lecule expression and monocyte adhesion. Taken together, these results demonstrate that increased endothelial PFKFB3 expression promotes diet-induced inflammatory responses and subsequent insulin resistance, suggesting that endothelial metabolic alteration plays an important role in the development of insulin resistance.

Original languageEnglish (US)
Pages (from-to)93-104
Number of pages12
JournalJournal of Endocrinology
Issue number3
StatePublished - Jul 1 2021


  • Endothelial cell
  • Inflammation
  • Insulin resistance
  • NF-κB
  • PFKFB3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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