Abstract
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.
Highlights
Adipose tissue contributes to the pathophysiology of a variety of cardiometabolic disorders, such as atherosclerosis, obesity, diabetes mellitus, and the metabolic syndrome [1]
This study gives clearer insights on the direct regulation exerted by D-Chiro-Inositol (D-Chiro-Ins) on human adipocytes differentiation, as well as its synergistic signaling activity with estrogen and with insulin
These results reinforce the hypothesis that the different D-Chiro-Ins clinical actions may depend on multiple targets, including the direct modulation of fat insulin signaling
Summary
Adipose tissue contributes to the pathophysiology of a variety of cardiometabolic disorders, such as atherosclerosis, obesity, diabetes mellitus, and the metabolic syndrome [1]. Several common conditions in women are influenced by the amount and biological activity of fat tissue, such as menstrual cycle disorders, infertility, polycystic ovary syndrome (PCOS) as well as gestational. The menopausal transition is characterized by prominent fat tissue changes, with visceral redistribution and increased metabolic perturbance [3]. Studies over the years have shown significant differences between men and women in fat distribution and function, suggesting the role of sex hormones. Women experience modifications in fat accumulation, distribution and metabolic activity: all these factors are closely related to hormonal levels’ changes in women, during pregnancy and menopause [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
