Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather than obesity in the mouse

Autor: Sergio Muñoz, Sebastián Cerdán, Ivet Elias, Tura Ferre, A. M. Monteys, Sylvie Franckhauser, Maria Molas, Antonio Hidalgo, Anna Pujol, Jesús Ruberte, Fatima Bosch
Přispěvatelé: Ministerio de Educación y Cultura (España), Generalitat de Catalunya, Instituto de Salud Carlos III, Federación Española de Enfermedades Raras, European Commission
Rok vydání: 2010
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1432-0428
Popis: [Aims/hypothesis]: In adipocytes, triacylglycerol synthesis depends on the formation of glycerol 3-phosphate, which originates either from glucose, through glycolysis, or from lactate, through glyceroneogenesis. However, glucose is traditionally viewed as the main precursor of the glycerol backbone and thus, enhanced glucose uptake would be expected to result in increased triacylglycerol synthesis and contribute to obesity. [Methods]: To further explore this issue, we generated a mouse model with chronically increased glucose uptake in adipose tissue by expressing Gck, which encodes the glucokinase enzyme. [Results]: Here we show that the production of high levels of glucokinase led to increased adipose tissue glucose uptake and lactate production, improved glucose tolerance and higher whole-body and skeletal muscle insulin sensitivity. There was no parallel increase in glycerol 3-phosphate synthesis in vivo, fat accumulation or obesity. Moreover, at high glucose concentrations, in cultured fat cells overproducing glucokinase, glycerol 3-phosphate synthesis from pyruvate decreased, while glyceroneogenesis increased in fat cells overproducing hexokinase II. [Conclusions/interpretations]: These findings indicate that the absence of glucokinase inhibition by glucose 6-phosphate probably led to increased glycolysis and blocked glyceroneogenesis in the mouse model. Furthermore, this study suggests that under physiological conditions, when blood glucose increases, glyceroneogenesis may prevail over glycolysis for triacylglycerol formation because of the inhibition of hexokinase II by glucose 6-phosphate. Together these results point to the indirect pathway (glucose to lactate to glycerol 3-phosphate) being key for fat deposition in adipose tissue. © 2010 Springer-Verlag.
S. Muñoz and A. Hidalgo received predoctoral fellowships from Direcció General d’Universitats, Generalitat de Catalunya, Spain. A. M. Monteys received a predoctoral fellowship from the Ministerio de Educación y Cultura, Spain. This study was supported by grants from Plan Nacional de I+D+I (SAF2002-20389 and SAF2005-01262) and Instituto de Salud Carlos III (CIBER de Diabetes y Enfermedades Metabólicas Asociadas), Spain and from the European Community (FP6 EUGENE2 [LSHM-CT-2004-512013]).
Databáze: OpenAIRE
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