Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Surgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2020 May;47(5):3459-3468. doi: 10.1007/s11033-020-05431-5. Epub 2020 Apr 10.
It is well-established that an impaired adipose tissue function and morphology caused by a dysregulated gene expression contribute substantially to obesity. Nowadays, animal model studies and in vitro surveys provide evidence for possible roles of HDACs as emerging epigenetic players in the pathogenesis of obesity. However, the clinical pertinence of HDACs in the field of obesity research in humans is not yet obvious. Here, we investigated mRNA expression of HDAC1, 3 and 9 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of obese female participants (n = 20) and normal-weight women (n = 19). We also evaluated the association of the afore-mentioned HDACs gene expression with obesity indices, insulin resistance parameters, and other obesity-related characteristics. Our data revealed the mRNA level of HDAC1 was significantly decreased in both VAT and SAT of obese women, compared to controls. Moreover, the SAT mRNA expression of HDAC3 and VAT mRNA levels of HDAC9 were significantly lower in obese subjects than those found in controls. We observed that HDAC1 and HDAC3 expression in adipose tissue from the whole population is inversely correlated with obesity indices; BMI, waist, hip and waist-to-height ratio (WHtR). Moreover, we found that HDAC3 expression in adipose tissue had an inverse correlation with HOMA-IR, insulin levels, and serum concentration of hs-CRP. Moreover, VAT HDAC9 mRNA level is inversely correlated with obesity indices; BMI, waist, hip and WHtR and with HOMA-IR, insulin levels, and serum concentration of hs-CRP. Hence, it seems that decreased HDAC1,3 and 9 mRNA expression in adipose tissue might be associated with obesity and related abnormalities. However, more studies are needed to establish this concept.
已有充分证据表明,基因表达失调导致的脂肪组织功能和形态受损,对肥胖的发生有重要作用。目前,动物模型研究和体外研究都为 HDAC 作为肥胖发病机制中新兴的表观遗传因子发挥可能的作用提供了证据。然而,在肥胖研究领域,HDAC 在人类中的临床相关性尚不清楚。在这里,我们研究了肥胖女性(n=20)和正常体重女性(n=19)内脏脂肪组织(VAT)和皮下脂肪组织(SAT)中 HDAC1、3 和 9 的 mRNA 表达。我们还评估了上述 HDAC 基因表达与肥胖指数、胰岛素抵抗参数和其他肥胖相关特征的相关性。我们的数据显示,与对照组相比,肥胖女性的 VAT 和 SAT 中 HDAC1 的 mRNA 水平显著降低。此外,肥胖组的 SAT 中 HDAC3 和 VAT 中 HDAC9 的 mRNA 水平均低于对照组。我们观察到,整个人群的脂肪组织中 HDAC1 和 HDAC3 的表达与肥胖指数呈负相关;BMI、腰围、臀围和腰高比(WHtR)。此外,我们发现脂肪组织中 HDAC3 的表达与 HOMA-IR、胰岛素水平和 hs-CRP 血清浓度呈负相关。此外,VAT HDAC9 的 mRNA 水平与肥胖指数呈负相关;BMI、腰围、臀围和 WHtR,以及 HOMA-IR、胰岛素水平和 hs-CRP 血清浓度。因此,脂肪组织中 HDAC1、3 和 9 的 mRNA 表达降低似乎与肥胖及其相关异常有关。然而,还需要更多的研究来确立这一概念。