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Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight.
- Source :
-
Diabetes [Diabetes] 2014 Jan; Vol. 63 (1), pp. 111-21. Date of Electronic Publication: 2013 Sep 23. - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Adipocytes cytology
Adult
Cells, Cultured
CpG Islands genetics
DNA Methylation
Fatty Acid-Binding Proteins genetics
Fatty Acid-Binding Proteins metabolism
Glucose Transporter Type 4 genetics
Glucose Transporter Type 4 metabolism
Humans
Infant, Newborn
Leptin metabolism
Male
PPAR gamma genetics
PPAR gamma metabolism
Promoter Regions, Genetic
Registries
Adipocytes metabolism
Adipogenesis genetics
Infant, Low Birth Weight metabolism
Leptin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 63
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 24062248
- Full Text :
- https://doi.org/10.2337/db13-0621