Dyslipidemia, insulin resistance, and impairment of placental metabolism in the offspring of obese mothers.
Dyslipidemia, insulin resistance, and impairment of placental metabolism in the offspring of obese mothers.
复制标题
DOI：
10.1017/s2040174420001026
复制
发表时间：
2021-10
影响因子：
1.7
通讯作者：
Maloyan A
中科院分区：
文献类型：
--
作者：
Bucher M;Montaniel KRC;Myatt L;Weintraub S;Tavori H;Maloyan A
肥胖是一种与血脂异常和胰岛素抵抗相关的慢性疾病。在这里，我们表明，肥胖母亲的后代从一开始就是血脂异常和胰岛素抵抗。足月剖腹产后收集母体血液、脐带血和胎盘组织。将患者分组为正常体重（NW，BMI = 18-24.9）或肥胖（OB，BMI ≥ 30），并按胎儿性别分开。我们测量了母亲和脐带血中的血脂、胰岛素和葡萄糖。胰岛素抵抗用HOMA-IR定量，胎盘脂质和能量代谢标志物及相关代谢物分别用western blot和代谢组学方法检测。对于OB妇女，母体和脐带血中的总胆固醇均降低，而HDL仅在脐带血中降低，与性别无关。在OB妇女所生的婴儿中，脐带血胰岛素和胰岛素抵抗增加。胎盘中能量和脂代谢调节因子PGC 1 α、SIRT 3、ERRα、CPT 1 α和CPT 2的表达随母亲肥胖而降低，且呈性别依赖性（P < 0.05）。代谢组学显示OB妇女胎盘中酰基肉毒碱C16：0、C18：2和C20：4水平较低，表明β-氧化减少。在OB胎盘中，谷氨酰胺、谷氨酸、α-酮戊二酸（αKG）和2-羟基戊二酸（2-HG）升高，谷氨酰胺/谷氨酸比值降低（P < 0.05），表明诱导谷氨酸转化为αKG以维持正常的代谢流。肥胖母亲的新生儿开始他们的生活血脂异常和胰岛素抵抗。如果不是遗传的，这种主要的代谢紊乱可能是由异常的胎盘代谢解释的，对后代的健康和福祉有潜在的长期不良后果。
Obesity is a chronic condition associated with dyslipidemia and insulin resistance. Here, we show that the offspring of obese mothers are dyslipidemic and insulin resistant from the outset. Maternal and cord blood and placental tissues were collected following C-section at term. Patients were grouped as being normal weight (NW, BMI = 18–24.9) or obese (OB, BMI ≥ 30), and separated by fetal sex. We measured plasma lipids, insulin, and glucose in maternal and cord blood. Insulin resistance was quantified using the HOMA-IR. Placental markers of lipid and energy metabolism and relevant metabolites were measured by western blot and metabolomics, respectively. For OB women, total cholesterol was decreased in both maternal and cord blood, while HDL was decreased only in cord blood, independent of sex. In babies born to OB women, cord blood insulin and insulin resistance were increased. Placental protein expression of the energy and lipid metabolism regulators PGC1α, and SIRT3, ERRα, CPT1α, and CPT2 decreased with maternal obesity in a sex-dependent manner (P < 0.05). Metabolomics showed lower levels of acylcarnitines C16:0, C18:2, and C20:4 in OB women’s placentas, suggesting a decrease in β-oxidation. Glutamine, glutamate, alpha-ketoglutarate (αKG), and 2-hydroxyglutarate (2-HG) were increased, and the glutamine-to-glutamate ratio decreased (P < 0.05), in OB placentas, suggesting induction of glutamate into αKG conversion to maintain a normal metabolic flux. Newly-born offspring of obese mothers begin their lives dyslipidemic and insulin resistant. If not inherited genetically, such major metabolic perturbations might be explained by abnormal placental metabolism with potential long-term adverse consequences for the offspring’s health and wellbeing.