Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Int J Obes (Lond). 2020 Mar;44(3):697-706. doi: 10.1038/s41366-020-0528-4. Epub 2020 Jan 21.
This study investigated depot-specific mRNA expression of uncoupling protein 1 (UCP1) in human white adipose tissue (WAT) and its association with obesity-related markers.
We recruited 39 normal-weight, 41 nondiabetic obese, and 22 diabetic obese women. We measured UCP1 mRNA expression in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated the associations between UCP1 mRNA expression in VAT and SAT, and obesity-related markers including mRNA expression of leptin, adiponectin, CCAAT-enhancer-binding protein homologous protein (CHOP), and positive regulatory domain-containing protein 16 (PRDM16). We also evaluated UCP1 mRNA expression in differentiated human white adipocytes after treatment with various stressors and metabolic improvement agents in vitro.
UCP1 mRNA in VAT was significantly higher than in SAT in all groups. UCP1 mRNA in SAT was negatively correlated with BMI, total abdominal fat area, visceral fat area, blood pressure, fasting glucose, insulin, HOMA-IR score, triglyceride, hsCRP, fasting leptin levels, and adipocyte size. UCP1 mRNA in SAT was positively correlated with fasting adiponectin levels. UCP1 mRNA in VAT was negatively correlated with visceral-to-subcutaneous fat ratio (VSR), fasting glucose, and triglyceride levels. In SAT, UCP1 mRNA was negatively correlated with mRNA expression of leptin and CHOP, and positively correlated with mRNA expression of adiponectin. The expression of PRDM16 was positively correlated with UCP1 mRNA in both VAT and SAT. UCP1 mRNA expression in differentiated human white adipocytes was significantly reduced after incubation with thapsigargin, tunicamycin, homocysteine, TNF-α, or IL-β, and significantly increased after incubation with exendin 4, dapagliflozin, and telmisartan.
This study demonstrated depot-specific mRNA expression of UCP1 and its association with obesity-related markers in human WAT. UCP1 mRNA in human white adipocytes was suppressed by inflammatory agents and enhanced by metabolic improvement agents. UCP1 in human WAT might participate in the pathogenesis of obesity-related metabolic diseases.
本研究旨在探讨人白色脂肪组织（WAT）中解偶联蛋白 1（UCP1）的组织特异性 mRNA 表达及其与肥胖相关标志物的关系。
我们招募了 39 名正常体重、41 名非糖尿病肥胖和 22 名糖尿病肥胖女性。我们测量了腹部内脏脂肪组织（VAT）和皮下脂肪组织（SAT）中的 UCP1 mRNA 表达，并研究了 VAT 和 SAT 中 UCP1 mRNA 表达与肥胖相关标志物（包括瘦素、脂联素、CCAAT 增强子结合蛋白同源蛋白（CHOP）和正调控域包含蛋白 16（PRDM16）的 mRNA 表达）之间的关系。我们还评估了体外各种应激和代谢改善剂处理后分化的人白色脂肪细胞中 UCP1 mRNA 的表达。
所有组中，VAT 中的 UCP1 mRNA 明显高于 SAT。SAT 中的 UCP1 mRNA 与 BMI、总腹部脂肪面积、内脏脂肪面积、血压、空腹血糖、胰岛素、HOMA-IR 评分、甘油三酯、hsCRP、空腹瘦素水平和脂肪细胞大小呈负相关。SAT 中的 UCP1 mRNA 与空腹脂联素水平呈正相关。VAT 中的 UCP1 mRNA 与内脏-皮下脂肪比（VSR）、空腹血糖和甘油三酯水平呈负相关。在 SAT 中，UCP1 mRNA 与瘦素和 CHOP 的 mRNA 表达呈负相关，与脂联素的 mRNA 表达呈正相关。PRDM16 的表达与 VAT 和 SAT 中 UCP1 mRNA 的表达呈正相关。在人白色脂肪细胞分化后，用他普西醌、衣霉素、同型半胱氨酸、TNF-α 或 IL-β 孵育后，UCP1 mRNA 的表达明显降低，用 exendin 4、达格列净和替米沙坦孵育后，UCP1 mRNA 的表达明显增加。
本研究表明人 WAT 中 UCP1 的组织特异性 mRNA 表达及其与肥胖相关标志物的关系。人白色脂肪细胞中的 UCP1 mRNA 被炎症因子抑制，被代谢改善剂增强。人 WAT 中的 UCP1 可能参与肥胖相关代谢性疾病的发病机制。
