Food deprivation induces adipose plasminogen activator inhibitor-1 (PAI-1) expression without accumulation of plasma PAI-1 in genetically obese and diabetic db/db mice.
Relationships between energy intake and fibrinolytic functions have been documented in detail. We evaluated food deprivation (FD) as a means of modulating fibrinolytic activity in genetically obese and diabetic db/db mice and in their lean counterparts. Twelve hours of FD induced considerable gene expression of plasminogen activator inhibitor-1 (PAI-1) in both epididymal (3.8-fold, p < 0.05) and intestinal (2.4-fold, p < 0.05) adipose tissues without affecting plasma PAI-1 levels in db/db mice, whereas the FD did not affect these parameters in wild-type mice. Importantly, 24 hours of FD increased the plasma PAI-1 content in wild-type (1.9-fold, p < 0.01) but not in db/db mice, although adipose PAI-1 mRNA levels were significantly increased in db/db mice. The plasma PAI-1 content significantly correlated with hepatic PAI-1 mRNA levels in wild-type (r = 0.84, p < 0.01) and in db/db (r = 0.63, p < 0.01) mice. However, plasma PAI-1 did not correlate with adipose PAI-1 expression in db/db mice, although adipose tissue in general is thought to be the principal site of PAI-1 production in obesity. Hepatic PAI-1 expression was closely correlated with serum levels of free fatty acids in wild-type (r = 0.72, p < 0.01), but not in db/db mice. Adipose PAI-1 expression significantly correlated with serum corticosterone levels in both genotypes (wild-type, r = 0.52, p < 0.05; db/db, r = 0.51, p < 0.01), suggesting that adipose PAI-1 expression is up-regulated by fasting-induced glucocorticoids. The present findings suggested that fasting differentially affects fibrinolytic activity in obese and lean subjects and that PAI-1 expression in the liver as well as in adipose tissues comprises an important determinant of increased risk for cardiovascular disease in obesity.
Oishi
Katsutaka
K
Clock Cell Biology Research Group, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Ohkura
Naoki
N
Matsuda
Juzo
J
Ishida
Norio
N
D000273:Adipose Tissue; D000821:Animal Feed; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000235:genetics*; D004822:Epididymis / Q000378:metabolism; D005508:Food Deprivation; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000097:blood* / Q000235:genetics; D054411:Receptors, Leptin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D054411:Receptors, Leptin