Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight.
Low birth weight (LBW) is associated with increased risk of the development of type 2 diabetes (T2D). The appetite-regulating hormone leptin is released from mature adipocytes, and its production may be decreased in immature preadipocytes from LBW individuals. We recruited 14 men born with LBW and 13 controls born with normal birth weight (NBW). Biopsy samples were obtained from subcutaneous abdominal fat depots, and preadipocytes were isolated and cultured. Gene expression of leptin and selected differentiation markers were analyzed during preadipocyte differentiation, and cell culture media were collected to analyze leptin secretion. DNA methylation of CpG sites in the leptin promoter was measured using pyrosequencing. We found that differentiating preadipocytes from LBW individuals showed reduced leptin gene expression and a corresponding reduced leptin release compared with NBW individuals. Mean DNA methylation of the proximal LEP promoter was increased in LBW compared with NBW individuals. The notion of impaired adipocyte maturation in LBW individuals was supported by a lower mRNA expression of the differentiation markers; fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, and GLUT4. Our findings are consistent with impaired preadipocyte maturation, contributing to an increased risk of the development of T2D in LBW subjects.
Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.
Ninna S
NS
Schultz
Christa
C
Broholm
Linn
L
Gillberg
Brynjulf
B
Mortensen
Sine W
SW
Jørgensen
Heidi S
HS
Schultz
Camilla
C
Scheele
Jørgen F P
JF
Wojtaszewski
Bente K
BK
Pedersen
Allan
A
Vaag
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism*; D007231:Infant, Newborn; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012042:Registries
C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D020738:Leptin; D047495:PPAR gamma; C495692:SLC2A4 protein, human