Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0399
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 9 5356-5360
Copyright © 2005 by The Endocrine Society
Upstream Transcription Factor-1 Gene Polymorphism Is Associated with Increased Adipocyte Lipolysis
Johan Hoffstedt,
Mikael Rydén,
Hans Wahrenberg,
Vanessa van Harmelen and
Peter Arner
Department of Medicine, Karolinska Institute, SE-141 86 Stockholm, Sweden
Address all correspondence and requests for reprints to: Dr. Johan Hoffstedt, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. E-mail: johan.hoffstedt{at}medhs.ki.se.
Objective: Variations in lipid metabolism between individuals could be due to genetic factors. A transmission of a haplotype of the upstream transcription factor-1 (USF-1) gene containing the minor alleles at the usf1s1 and usfs2 loci is described. We investigated whether these polymorphisms are associated with adipocyte lipolysis.
Methods and Results: A total of 196 healthy obese women were investigated for in vitro lipolysis regulation in sc fat cells, which was set in relation to the usf1s1 C
T and usf1s2 GA polymorphisms in the usf1 gene. The two polymorphisms were in complete linkage disequilibrium. The usf1s1/2 T/A allele was associated with increases in the maximum lipolytic action of noradrenaline (P = 0.005), dobutamine (P = 0.008), terbutaline (P = 0.008), CGP12177 (P = 0.015), and forskolin (P = 0.006). In contrast, no significant genotype effect on lipolytic sensitivity (i.e. half-maximum effective concentration) for any of the drugs was demonstrated. Analysis of adipose tissue mRNA expression in 78 women from genes regulating lipolysis at the postadrenoceptor level showed an increased level of protein kinase A subunit R1
in the T/A genotype (P = 0.02).
Conclusions: Polymorphism in the usf1 gene is associated with increased lipolytic effect of catecholamines in fat cells, which is localized at the postadrenoceptor level, possibly, at least, involving protein kinase A.
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Copyright © 2005 by The Endocrine Society
