Guo, Xin (2013-05). A Role for PFKFB3/IPFK2 in Overnutrition-Associated Adipose Tissue and Intestine Inflammatory Responses and Insulin Resistance. Doctoral Dissertation. Thesis uri icon

abstract

  • Overnutrition causes many metabolic diseases including type 2 diabetes. PFKFB3/iPFK2 is a master regulator of adipocyte and intestinal nutrient metabolism. Using PFKFB3/iPFK2+/- mice and adipocyte-specific PFKFB3 over-expression mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity, inflammation in adipose tissue and intestine, and systemic insulin resistance. On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. However, HFD-induced systemic insulin resistance in PFKFB3+/- mice was more severe than in wild-type littermates. In contrast, adipocyte-specific PFKFB3 over-expression increased adiposity but suppressed overnutrition induced adipose tissue inflammatory response and improved insulin sensitivity. In addition to adipose tissue, PFKFB3/iPFK2 also played a role in intestine events. Compared to wild-type littermates, PFKFB3+/- mice displayed a significant increase in the expression of intestinal inflammatory markers on a HFD. In conclusion, PFKFB3 protects against overnutrition-induced adipose tissue and intestine inflammatory response and systemic insulin resistance in an adiposity-independent manner. Selective PFKFB3 activation may be viable for treating and/or preventing insulin resistance and type 2 diabetes.
  • Overnutrition causes many metabolic diseases including type 2 diabetes. PFKFB3/iPFK2 is a master regulator of adipocyte and intestinal nutrient metabolism. Using PFKFB3/iPFK2+/- mice and adipocyte-specific PFKFB3 over-expression mice, the present study investigated the role of PFKFB3/iPFK2 in regulating diet-induced adiposity, inflammation in adipose tissue and intestine, and systemic insulin resistance.

    On a high-fat diet (HFD), PFKFB3+/- mice gained much less body weight than did wild-type littermates. However, HFD-induced systemic insulin resistance in PFKFB3+/- mice was more severe than in wild-type littermates. In contrast, adipocyte-specific PFKFB3 over-expression increased adiposity but suppressed overnutrition induced adipose tissue inflammatory response and improved insulin sensitivity. In addition to adipose tissue, PFKFB3/iPFK2 also played a role in intestine events. Compared to wild-type littermates, PFKFB3+/- mice displayed a significant increase in the expression of intestinal inflammatory markers on a HFD.

    In conclusion, PFKFB3 protects against overnutrition-induced adipose tissue and intestine inflammatory response and systemic insulin resistance in an adiposity-independent manner. Selective PFKFB3 activation may be viable for treating and/or preventing insulin resistance and type 2 diabetes.

ETD Chair

publication date

  • May 2013