PURPOSE: Excessive fructose intake coincides with the growing rate of obesity and metabolic syndrome, with women being more prone to these disorders than men. Findings that detrimental effects of fructose might be mediated by glucocorticoid regeneration in adipose tissue only indirectly implicated glucocorticoid receptor (GR) in the phenomenon. The aim of the present study was to elucidate whether fructose overconsumption induces derangements in GR expression and function that might be associated with fructose-induced adiposity in females. METHODS: We examined effects of fructose-enriched diet on GR expression and function in visceral adipose tissue of female rats. Additionally, we analyzed the expression of genes involved in glucocorticoid prereceptor metabolism [11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase], lipolysis (hormone-sensitive lipase) and lipogenesis (sterol regulatory element binding protein 1 and peroxisomal proliferator-activated receptor γ). RESULTS: Fructose-fed rats had elevated energy intake that resulted in visceral adiposity, as indicated by increased visceral adipose tissue mass and its share in the whole-body weight. GR hormone binding capacity and affinity, as well as the expression of GR gene at both mRNA and protein levels were reduced in visceral adipose tissue of the rats on fructose diet. The glucocorticoid prereceptor metabolism was stimulated, as evidenced by elevated tissue corticosterone, while the key regulators of lipolysis and lipogenesis remained unaffected by fructose diet. CONCLUSIONS: The results suggest that the 11βHSD1-mediated elevation of intracellular corticosterone may induce GR downregulation, which may be associated with failure of GR to stimulate lipolysis in fructose-fed female rats.
PURPOSE: Excessive fructose intake coincides with the growing rate of obesity and metabolic syndrome, with women being more prone to these disorders than men. Findings that detrimental effects of fructose might be mediated by glucocorticoid regeneration in adipose tissue only indirectly implicated glucocorticoid receptor (GR) in the phenomenon. The aim of the present study was to elucidate whether fructose overconsumption induces derangements in GR expression and function that might be associated with fructose-induced adiposity in females. METHODS: We examined effects of fructose-enriched diet on GR expression and function in visceral adipose tissue of female rats. Additionally, we analyzed the expression of genes involved in glucocorticoid prereceptor metabolism [11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase], lipolysis (hormone-sensitive lipase) and lipogenesis (sterol regulatory element binding protein 1 and peroxisomal proliferator-activated receptor γ). RESULTS:Fructose-fed rats had elevated energy intake that resulted in visceral adiposity, as indicated by increased visceral adipose tissue mass and its share in the whole-body weight. GR hormone binding capacity and affinity, as well as the expression of GR gene at both mRNA and protein levels were reduced in visceral adipose tissue of the rats on fructose diet. The glucocorticoid prereceptor metabolism was stimulated, as evidenced by elevated tissue corticosterone, while the key regulators of lipolysis and lipogenesis remained unaffected by fructose diet. CONCLUSIONS: The results suggest that the 11βHSD1-mediated elevation of intracellular corticosterone may induce GR downregulation, which may be associated with failure of GR to stimulate lipolysis in fructose-fed female rats.
Authors: Nicholas M Morton; Janice M Paterson; Hiroaki Masuzaki; Megan C Holmes; Bart Staels; Catherine Fievet; Brian R Walker; Jeffrey S Flier; John J Mullins; Jonathan R Seckl Journal: Diabetes Date: 2004-04 Impact factor: 9.461
Authors: Juan Pablo Fariña; María Elisa García; Ana Alzamendi; Andrés Giovambattista; Carlos Alberto Marra; Eduardo Spinedi; Juan José Gagliardino Journal: Clin Sci (Lond) Date: 2013-07-01 Impact factor: 6.124
Authors: Hiroaki Masuzaki; Hiroshi Yamamoto; Christopher J Kenyon; Joel K Elmquist; Nicholas M Morton; Janice M Paterson; Hiroshi Shinyama; Matthew G F Sharp; Stewart Fleming; John J Mullins; Jonathan R Seckl; Jeffrey S Flier Journal: J Clin Invest Date: 2003-07 Impact factor: 14.808
Authors: S S Loza-Medrano; L A Baiza-Gutman; L Manuel-Apolinar; R García-Macedo; L Damasio-Santana; O A Martínez-Mar; M C Sánchez-Becerra; M Cruz-López; M A Ibáñez-Hernández; M Díaz-Flores Journal: Mol Biol Rep Date: 2019-10-24 Impact factor: 2.316
Authors: J H Goedecke; E Chorell; D E W Livingstone; R H Stimson; P Hayes; K Adams; J A Dave; H Victor; N S Levitt; S E Kahn; J R Seckl; B R Walker; T Olsson Journal: Int J Obes (Lond) Date: 2014-05-20 Impact factor: 5.095