AN
2001:508352 BIOSIS
DN
PREV200100508352
TI
A common hormone-sensitive lipase i6 gene polymorphism is associated
with decreased human adipocyte lipolytic function.
AU
Hoffstedt, Johan [Reprint author]; Arner, Peter; Schalling, Martin;
Pedersen, Nancy L.; Sengul, Selim; Ahlberg, Susanne; Iliadou, Anastasia;
Lavebratt, Catharina
CS
Karolinska Institutet, Huddinge University Hospital, CME, M61, 141 86,
Stockholm, Sweden
johan.hoffstedt@medhs.ki.se
SO
Diabetes, (October, 2001) Vol. 50, No. 10, pp. 2410-2413. print.
CODEN: DIAEAZ. ISSN: 0012-1797.
DT
Article
LA
English
ED
Entered STN: 31 Oct 2001
Last Updated on STN: 23 Feb 2002
AB
Hereditary factors may be involved in the pathogenesis of type 2
diabetes. A polymorphism in the hormone-sensitive lipase (HSL)
gene (HSLi6) is associated with obesity and diabetes, although it is
unknown whether the polymorphism is functional and thereby influences
lipolysis. We genotyped 355 apparently healthy non-obese male and female
subjects for the HSLi6 polymorphism. Allele 5 was found to be the most
common allele (allele frequency 0.57). In 117 of the subjects, we
measured abdominal subcutaneous fat cell lipolysis induced by drugs acting
at various steps in the lipolytic cascade. The lipolysis rate induced by
norepinephrine isoprenaline (acting on beta-adrenoceptors), forskolin
(acting on adenylyl cyclase), and dibutyryl cyclic AMP (acting on HSL)
were all decreased by apprx50% in allele 5 homozygotes, as compared with
noncarriers. Heterozygotes showed an intermediate lipolytic rate. The
difference in lipolysis rate between genotypes was more pronounced in men
than in women. We conclude that allele 5 of the HSLi6 polymorphism is
associated with a marked decrease in the lipolytic rate of abdominal fat
cells. This may in turn contribute to the development of obesity.
CC
Genetics - Human 03508
Metabolism - General metabolism and metabolic pathways 13002
Metabolism - Metabolic disorders 13020
Endocrine - General 17002
IT
Major Concepts
Clinical Endocrinology (Human Medicine, Medical Sciences); Medical
Genetics (Allied Medical Sciences); Metabolism
IT
Diseases
obesity: nutritional disease
Obesity (MeSH)
IT
Diseases
type II diabetes: metabolic disease
Diabetes Mellitus, Non-Insulin-Dependent (MeSH)
IT
Miscellaneous Descriptors
lipolysis
ORGN
Classifier
Hominidae 86215
Super Taxa
Primates; Mammalia; Vertebrata; Chordata; Animalia
Organism Name
human: female, male, patient
Taxa Notes
Animals, Chordates, Humans, Mammals, Primates, Vertebrates
GEN
human HSL gene [human hormone-sensitive lipase gene] (Hominidae)