Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis.
OBJECTIVE
We investigated the role of the adipocyte-specific protein perilipin for lipolysis in humans.


METHODS
Perilipin protein content and lipolysis rates were measured in human subcutaneous fat cells of non-obese (n=10) and obese (n=117) women. Single nucleotide polymorphisms in the perilipin gene were examined in obese subjects.


RESULTS
Basal and noradrenaline-induced rates of lipolysis were two to fourfold increased (p<0.01) and perilipin protein content decreased 50% (p=0.005) in adipocytes of the obese women. In subjects matched for body mass index and fat-cell volume, a high rate of lipolysis was associated with a low adipocyte content of perilipin (p=0.01). Adipocyte content of perilipin was inversely correlated with the circulating concentrations of glycerol (r=0.62) and non-esterified fatty acids (n=0.49). A gene polymorphism (rs891460 A/G) in intron 6 was common. In AA subjects basal and noradrenaline induced lipolysis were 50 to 100% times more rapid (p</=0.01) and the adipocyte perilipin content was about 80% reduced (p=0.005) as compared to GG carriers. Intermediate values were found in AG carriers.


CONCLUSIONS
Perilipin seems important for the regulation of lipolysis in human fat cells. Obesity and a polymorphism in the perilipin gene associate with decreased protein content of perilipin and increased basal (unstrained) and noradrenaline-induced lipolysis. Low perilipin content also associate with high in vivo lipolytic activity. Perilipin could be a factor behind impaired lipolysis in insulin-resistant conditions.
Mottagui-Tabar
S
S
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Rydén
M
M
Löfgren
P
P
Faulds
G
G
Hoffstedt
J
J
Brookes
A J
AJ
Andersson
I
I
Arner
P
P
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002352:Carrier Proteins; D048429:Cell Size; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008066:Lipolysis / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002352:Carrier Proteins; D017931:DNA Primers; D007328:Insulin; D000070778:Perilipin-1; D010750:Phosphoproteins; D014280:Triglycerides; D002784:Cholesterol