Steno Diabetes Center Copenhagen, Herlev, Denmark.
Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
Eur J Endocrinol. 2022 Mar 25;186(5):511-521. doi: 10.1530/EJE-21-1221.
Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors.
Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD).
The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups.
Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.
由于皮下脂肪组织扩张能力受损而导致的肝外脂肪沉积，可能代表了一种与低出生体重（LBW）相关的关键特征，即增加 2 型糖尿病（T2D）的风险。我们研究了假定健康的早中年、非肥胖 LBW 受试者是否表现出肝内脂肪含量增加，以及 LBW 中肝内脂肪增加是否与代谢异常特征的严重程度相关，最后，这些关联是否可能受到遗传因素的影响。
使用 1H 磁共振波谱，我们测量了 26 名早中年、非肥胖 LBW 和 22 名 BMI 匹配的正常出生体重（NBW）男性的肝内脂肪含量。通过稳定同位素测量内源性葡萄糖生成，通过多重 ELISA 测量一系列血浆脂肪因子和肠道激素分析物。从与出生体重、身高、T2D、血浆胆固醇和非酒精性脂肪肝（NAFLD）风险基因型相关的全基因组关联研究（GWAS）数据中计算遗传风险评分。
LBW 受试者的肝内脂肪含量明显高于 NBW 对照组（P=0.014），20%的 LBW 受试者有明显的 NAFLD。与 NBW 和 LBW 无 NAFLD 个体相比，LBW 合并 NAFLD 受试者表现出广泛的代谢变化，包括肝胰岛素抵抗、血浆脂肪因子和肠道激素紊乱以及血脂异常。作为一个例外，与 NBW 对照组相比，LBW 受试者无论是否合并 NAFLD，其血浆脂联素水平均较低。选择的差异特征的遗传风险在各组之间没有差异。
包括明显的 NAFLD 在内的肝内脂肪含量增加，可能是非遗传方式将 LBW 与 T2D 风险增加联系起来的关键途径。
