Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight
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Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight. / Schultz, Ninna S; Broholm, Christa; Gillberg, Linn; Mortensen, Brynjulf; Jørgensen, Sine W; Schultz, Heidi Schiøler; Scheele, Camilla; Wojtaszewski, Jørgen; Pedersen, Bente Klarlund; Vaag, Allan.
In: Diabetes, Vol. 63, No. 1, 2014, p. 111-121.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight
AU - Schultz, Ninna S
AU - Broholm, Christa
AU - Gillberg, Linn
AU - Mortensen, Brynjulf
AU - Jørgensen, Sine W
AU - Schultz, Heidi Schiøler
AU - Scheele, Camilla
AU - Wojtaszewski, Jørgen
AU - Pedersen, Bente Klarlund
AU - Vaag, Allan
N1 - CURIS 2014 NEXS 005
PY - 2014
Y1 - 2014
N2 - Low birth weight (LBW) is associated with increased risk of developing 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). Biopsies 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 was 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 to NBW individuals. Mean DNA methylation of the proximal LEP promoter was increased in LBW compared to 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 (FABP4), peroxisome proliferator-activated receptor γ (PPARγ), and glucose transporter type 4 (GLUT4). Our findings are consistent with impaired preadipocyte maturation contributing to increased risk of developing T2D in LBW subjects.
AB - Low birth weight (LBW) is associated with increased risk of developing 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). Biopsies 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 was 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 to NBW individuals. Mean DNA methylation of the proximal LEP promoter was increased in LBW compared to 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 (FABP4), peroxisome proliferator-activated receptor γ (PPARγ), and glucose transporter type 4 (GLUT4). Our findings are consistent with impaired preadipocyte maturation contributing to increased risk of developing T2D in LBW subjects.
U2 - 10.2337/db13-0621
DO - 10.2337/db13-0621
M3 - Journal article
C2 - 24062248
VL - 63
SP - 111
EP - 121
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -
ID: 51230433