A role of PFKFB3/iPFK2 in the regulation of high fat diet‐induced inflammation and metabolic responses

Abstract

Feeding of a high fat diet (HFD) is shown to induce inflammation and dysregulated metabolic homeostasis. Here we show that PFKFB3, a gene whose product controls glycolysis, plays a pivotal role in the regulation of HFD‐induced inflammatory and metabolic responses. Upon feeding a HFD, C57BL6 wild‐type mice exhibit a significant increase in body weight, which is associated with increased fat accumulation in both the liver and adipose tissue. This weight gain‐effect of HFD feeding is significantly lessened in mice that lack one allele of PFKFB3 (PFKFB3+/− mice). In addition, there are no increases in fat accumulation in both the liver and adipose tissue of HFD‐fed PFKFB3+/− mice. However, compared to HFD‐fed wild‐type mice, HFD‐fed PFKFB3+/− mice exhibited a greater increase in tumor necrosis factor α(TNFα) and interleukin 6 (IL6) expression in both the liver and adipose tissue, indicating elevated inflammation. Moreover, plasma levels of glucose in HFD‐fed PFKFB3+/− mice are much higher than those in HFD‐fed wild‐type control mice, which are accompanied by exacerbated glucose intolerance and insulin resistance. Together, these findings demonstrate that PFKFB3 is crucial for the regulation of HFD‐induced inflammation and dysregulated metabolic homeostasis. Approaches that stimulate PFKFB3 expression may be viable to prevent or treat diabetes.Grant Funding Sourcenone