Upstream transcription factor-1 gene polymorphism is associated with increased adipocyte lipolysis.
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.


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 G-->A 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 R1alpha 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.
Hoffstedt
Johan
J
Department of Medicine, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. johan.hoffstedt@medhs.ki.se
Rydén
Mikael
M
Wahrenberg
Hans
H
van Harmelen
Vanessa
V
Arner
Peter
P
D000225:Adenine; D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003596:Cytosine; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008066:Lipolysis / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism / Q000473:pathology; D013941:Thymine; D014157:Transcription Factors / Q000235:genetics*; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine