Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Gynecological Endocrinology Center, Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy.
Front Endocrinol (Lausanne). 2021 Mar 30;12:660815. doi: 10.3389/fendo.2021.660815. eCollection 2021.
D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins's actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson-Golabi-Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.
D-手性肌醇（D-Chiro-Ins）是胰岛素信号通路中的一种二级信使。D-Chiro-Ins 调节胰岛素分泌、线粒体呼吸链和糖原储存。由于这些作用，D-Chiro-Ins 被提议纠正各种代谢功能障碍情况下的胰岛素功能缺陷，例如多囊卵巢综合征（PCOS）、肥胖、妊娠糖尿病和绝经后脂肪堆积。由于不清楚 D-Chiro-Ins 是否直接作用于脂肪细胞，我们旨在使用源自 Simpson-Golabi-Behmel 综合征（SGBS）的人脂肪细胞系研究 D-Chiro-Ins 对脂肪细胞活力、增殖、分化和胰岛素相关蛋白表达的作用，该细胞系可完全分化为成熟脂肪细胞。在整个分化过程中，用 D-Chiro-Ins、17β-雌二醇（E2）或胰岛素处理细胞。D-Chiro-Ins 对细胞活力和增殖没有影响，然后 D-Chiro-Ins 仅在最后几天的过程中促进细胞分化，而 E2 则从第一阶段开始增强分化。D-Chiro-Ins 刺激脂质储存和大脂质滴的产生，从而减少游离脂肪酸的含量。我们还发现，D-Chiro-Ins 单独或与胰岛素和 E2 一起增加胰岛素受体底物-1（IRS1）和葡萄糖转运蛋白 4（GLUT4）的表达和激活。总之，这项工作表明 D-Chiro-Ins 在人类脂肪细胞的分化和功能中发挥直接作用，它通过招募参与脂质和葡萄糖储存的信号转导途径与胰岛素和雌激素协同作用。这些发现为更好地理解 D-Chiro-Ins 在生理和各种疾病中对女性脂肪代谢的作用提供了明确的见解。
