Systems Biology Group Lab, 00161 Rome, Italy.
Experts Group on Inositols in Basic and Clinical Research (EGOI), 00161 Rome, Italy.
Int J Mol Sci. 2023 Apr 18;24(8):7421. doi: 10.3390/ijms24087421.
White adipose tissue/brown adipose tissue trans-differentiation is one of the main study targets for therapies against obesity and metabolic diseases. In recent years, numerous molecules able to induce such trans-differentiation have been identified; however, their effect in obesity therapies has not been as expected. In the present study, we investigated whether myo-inositol and its stereoisomer D-chiro-inositol could be involved in the browning of white adipose tissue. Our preliminary results clearly indicate that both, at 60 μM concentration, induce the upregulation of uncoupling protein 1 mRNA expression, the main brown adipose tissue marker, and increase mitochondrial copy number as well as oxygen consumption ratio. These changes demonstrate an activation of cell metabolism. Therefore, our results show that human differentiated adipocytes (SGBS and LiSa-2), assume the features typical of brown adipose tissue after both treatments. Furthermore, in the cell lines examined, we proved that D-chiro-inositol and myo-Inositol induce an increase in the expression of estrogen receptor mRNAs, suggesting a possible modulation by these isomers. We also found an increase in the mRNA of peroxisome proliferator-activated receptor gamma, a very important target in lipid metabolism and metabolic diseases. Our results open new opportunities for the use of inositols in therapeutic strategies to counteract obesity and its metabolic complications.
白色脂肪组织/棕色脂肪组织转分化是肥胖症和代谢性疾病治疗的主要研究目标之一。近年来,已经鉴定出许多能够诱导这种转分化的分子;然而,它们在肥胖症治疗中的效果并不如预期。在本研究中,我们研究了肌醇及其立体异构体 D-手性肌醇是否参与白色脂肪组织的褐色化。我们的初步结果清楚地表明,在 60 μM 浓度下,两者均能上调解偶联蛋白 1 mRNA 的表达,这是棕色脂肪组织的主要标志物,并增加线粒体拷贝数和耗氧量比。这些变化表明细胞代谢被激活。因此,我们的结果表明,人分化脂肪细胞(SGBS 和 LiSa-2)在两种处理后呈现出典型的棕色脂肪组织特征。此外,在研究的细胞系中,我们证明 D-手性肌醇和肌醇诱导雌激素受体 mRNAs 的表达增加,表明这些异构体可能存在调节作用。我们还发现过氧化物酶体增殖物激活受体 γ 的 mRNA 增加,这是脂质代谢和代谢性疾病的一个非常重要的靶点。我们的结果为肌醇在对抗肥胖及其代谢并发症的治疗策略中的应用开辟了新的机会。