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 individualscould be due to genetic factors. A transmission of a haplotypeof the upstream transcription factor-1 (USF-1) gene containingthe minor alleles at the usf1s1 and usfs2 loci is described.We investigated whether these polymorphisms are associated withadipocyte lipolysis.
Methods and Results: A total of 196 healthy obese women wereinvestigated for in vitro lipolysis regulation in sc fat cells,which was set in relation to the usf1s1 CT and usf1s2 GA polymorphismsin the usf1 gene. The two polymorphisms were in complete linkagedisequilibrium. The usf1s1/2 T/A allele was associated withincreases 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 significantgenotype effect on lipolytic sensitivity (i.e. half-maximumeffective concentration) for any of the drugs was demonstrated.Analysis of adipose tissue mRNA expression in 78 women fromgenes regulating lipolysis at the postadrenoceptor level showedan increased level of protein kinase A subunit R1 in the T/Agenotype (P = 0.02).
Conclusions: Polymorphism in the usf1 gene is associated withincreased lipolytic effect of catecholamines in fat cells, whichis localized at the postadrenoceptor level, possibly, at least,involving protein kinase A.
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T and usf1s2 G
in the T/A genotype (P = 0.02). 
