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Rosiglitazone controls fatty acid cycling by means of glyceroneogenesis and glycerol phosphorylation
Author(s) -
Leroyer Stéphanie,
Chauvet Geneviève,
Tordjman Joan,
Quette Joëlle,
Chapron Charles,
Forest Claude,
Antoine Bénédicte
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a957
Subject(s) - lipolysis , glycerol , adipose tissue , endocrinology , medicine , phosphoenolpyruvate carboxykinase , chemistry , rosiglitazone , phosphorylation , insulin resistance , fatty acid , biochemistry , enzyme , insulin
A sustained increase in circulating fatty acids (FA) can cause insulin resistance. Plasma FA level depends on triglycerides (TG) lipolysis and FA re‐esterification within fat cells. Whereas participation of two complementary pathways, glyceroneogenesis (GNG) and glycerol phosphorylation (GP), to FA re‐esterification in response to rosiglitazone (Rosi) was functionally proved in rodents (Tordjman et al, JBC, 2003), it was only assumed in humans by means of induced phosphoenolpyruvate carboxykinase (PEPCK‐c) and glycerol kinase (GyK) gene expression. We studied GNG and GP involvement in FA re‐esterification in 16 subcutaneous adipose tissue samples from lean and obese women. After treatment with Rosi for three days, we monitored the specific activities of GNG and GP step‐limiting enzymes, PEPCK‐c and GyK, the incorporation of radiolabelled glycerol‐3‐P precursors, pyruvate and glycerol, into TG during a 1 hour‐long lipolysis and glycerol and FA concentrations in the culture medium. We showed that, in response to Rosi, increase in FA re‐esterification is strictly correlated to that in PEPCK‐c and GyK. While GNG Rosi‐responsiveness is rather constant according to women BMI, GP is only enhanced by Rosi in lean women. Hence, we demonstrate that GNG is the major pathway for FA re‐esterification in human subcutaneous adipose tissue and that it can be enhanced by supraphysiological concentrations of pyruvate. GP becomes an important complementary target of the hypolipidemic action of Rosi in lean women. In conclusion, our data suggest that Rosi should be preferentially given to lean people exhibiting a high risk of type 2 diabetes.