Department of Obstetrics and Gynecology, Stanford Health Care-ValleyCare Hospital, 5555 W. Las Positas Blvd, Pleasanton, CA, USA.
Department of Obstetrics and Gynecology, Center for Androgen-Related Disorders, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hum Reprod. 2019 Feb 1;34(2):335-344. doi: 10.1093/humrep/dey356.
Are non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)?
Women with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels.
Elevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown.
STUDY DESIGN, SIZE, DURATION: We prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]).
The study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects.
LIMITATIONS, REASONS FOR CAUTION: Our study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size.
Dysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare.
Not applicable.
多囊卵巢综合征（PCOS）患者的非酯化脂肪酸（NEFA）动力学是否发生改变？
患有 PCOS 的女性，特别是肥胖者，其血浆 NEFA 动力学对血浆胰岛素和葡萄糖水平的变化反应失调，这种变化与胰岛素抵抗（IR）有关，与空腹血浆 NEFA 水平无关。
许多疾病中，升高的血浆 NEFA 水平与 IR 有关，尽管 PCOS 患者的 NEFA 动力学的动态平衡及其与 IR 的关系尚不清楚。
研究设计、规模、持续时间：我们前瞻性地比较了 29 名 PCOS 患者和 29 名匹配 BMI 的健康对照女性的胰岛素敏感性和 NEFA 动力学。
参与者/材料、地点、方法：本研究在一所三级机构进行。在改良的频繁采样静脉葡萄糖耐量试验（mFSIVGTT）期间评估血浆 NEFA、葡萄糖和胰岛素水平。使用最小模型评估胰岛素敏感性（Si）和 NEFA 动力学（即模型衍生的初始血浆 NEFA 水平[NEFA0]、phi 常数[Φ]，反映葡萄糖介导的脂肪分解抑制以及脂肪组织最大脂解率[SFFA]和从血浆摄取 NEFA [KFFA]的测量值）。
该研究提供了新的证据，表明 PCOS 患者的 NEFA 动力学存在缺陷，表现为：（i）直接和模型测量的基础血浆 NEFA 水平较低（NEFA0），以及 （ii）在远程或间质空间中葡萄糖介导的脂肪分解抑制增强（反映为亲和力常数[Φ]降低）。然而，脂肪组织脂解的最大速率（SFFA）和从血浆中摄取 NEFA 的速率（KFFA）没有差异。在肥胖的 PCOS 患者中，观察到的 NEFA 动力学差异加剧，几乎仅观察到这种差异。
局限性、谨慎的原因：我们的研究没有研究 NEFA 亚型。它也是横断面的，基于在临床环境中定义的 1990 年美国国立卫生研究院（NIH）标准（即表型 A 和 B）和确定的 PCOS 患者。因此，应谨慎将本研究数据外推至 PCOS 的其他表型。此外，我们的数据是探索性的，因此需要更大的样本量进行验证。
NEFA 动力学的功能障碍可能是肥胖的非糖尿病 PCOS 女性代谢功能障碍的标志物，并且可能比简单地评估单次循环 NEFA 水平更重要，对于理解 PCOS 中 IR 的机制至关重要。
研究资金/竞争利益：这项工作得到了 NIH 授予 R01-DK073632 和 R01-HD29364 给 R.A.的资助；MD Medical Group、莫斯科、RF 的职业发展奖，D.L.和奥古斯塔大学的资金给 Y.-H.C.。RA 担任 Ansh Labs、Medtronics、Spruce Biosciences 和 Latitude Capital 的顾问。U.E.、Z.A.、D.L.、R.M.、Y.-H.C.、R.C.B.和 Y.D.I.C.没有利益冲突需要申报。
不适用。
