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- Title
Increased Glucose Uptake by Adipose Tissue Expression of Glucokinase in Transgenic Mice Leads to Lactate Production Rather than Fat Accumulation.
- Authors
Franckhauser, Sylvie; Muñoz, Sergio; Hidalgo, Antonio; Ferré, Tura; Mas, Alex; Elias, Ivet; Cerdáa, Sebastián; Pujol, Anna; Bosch, Fatima
- Abstract
In adipocytes, glucose is traditionally viewed as the main precursor of the glycerol backbone for triglyceride synthesis, although an alternative pathway, glyceroneogenesis, may also provide glycerol-3-phosphate. To examine whether increased glucose uptake in adipose tissue leads to obesity, mice were engineered to increase glucose phosphorylation in this tissue by expressing the hepatic glucokinase enzyme (GK). Transgenic mice expressed high levels of GK which led to increased adipose tissue glucose uptake, improved glucose tolerance and insulin sensitivity. However, glycerol-3-phosphate synthesis and body fat content were not altered in these mice. In contrast, alter a glucose load, adipose tissue from transgenic mice produced higher amounts of lactate as shown by nuclear magnetic resonance studies in vivo, and also in cultured fat pads. This resulted in an increase in circulating lactate levels. Nevertheless, transgenic mice were normoglycemic and normoinsulinemic. Thus, an increase in glycolytic flux in these transgenic mice led to lactate production, whereas we have previously shown that an increase in glyceroneogenesis leads to higher glycerol-3-phosphate synthesis and fat accumulation. This suggests that an increase in glucose uptake by adipose tissue may not lead to obesity. Moreover, our results suggest that glucose may not be the main precursor of glycerol-3-phosphate and that glyceroneogenesis may have a prominent role in triglyceride formation and in obesity.
- Subjects
BLOOD sugar; ADIPOSE tissues; GLUCOKINASE; LACTATES; OBESITY; TRIGLYCERIDES; TRANSGENIC mice
- Publication
Diabetes, 2007, Vol 56, pA458
- ISSN
0012-1797
- Publication type
Article