Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.
Diabetes. 2014 Jan;63(1):111-21. doi: 10.2337/db13-0621. Epub 2013 Sep 23.
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.
低出生体重（LBW）与 2 型糖尿病（T2D）发展风险增加有关。调节食欲的激素瘦素由成熟脂肪细胞释放，而 LBW 个体不成熟的前体脂肪细胞中瘦素的产生可能会减少。我们招募了 14 名出生时体重不足（LBW）的男性和 13 名出生时体重正常（NBW）的对照者。从腹部皮下脂肪组织中获取活检样本，并分离和培养前体脂肪细胞。分析前体脂肪细胞分化过程中瘦素和选定分化标志物的基因表达，并收集细胞培养物上清液分析瘦素分泌。使用焦磷酸测序测量瘦素启动子中 CpG 位点的 DNA 甲基化。我们发现，与 NBW 个体相比，LBW 个体的分化前体脂肪细胞中瘦素基因表达降低，相应的瘦素释放减少。与 NBW 个体相比，LBW 个体的近端 LEP 启动子的平均 DNA 甲基化增加。LBW 个体中脂肪酸结合蛋白 4、过氧化物酶体增殖物激活受体 γ 和 GLUT4 等分化标志物的 mRNA 表达较低，这一观点支持脂肪细胞成熟受损的观点。我们的发现与前体脂肪细胞成熟受损一致，这导致 LBW 受试者患 T2D 的风险增加。
