Targeted Overexpression of Inducible 6-phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects Against Diet-induced Insulin Resistance and Inflammatory Responses

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 May 5

PMID 22556414

Citations 37

Authors

Yuqing Huo

Xin Guo

Honggui Li

Hang Xu

Vera Halim

Weiyu Zhang

Huan Wang

Yang-Yi Fan

Kuok Teong Ong

Shih-Lung Woo

Robert S Chapkin

Douglas G Mashek

Yanming Chen

Hui Dong

Fuer Lu

Lai Wei

Chaodong Wu

Affiliations

Soon will be listed here.

Abstract

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues.

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