Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Endocrinology, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou China.
J Ethnopharmacol. 2025 Jan 10;336:118760. doi: 10.1016/j.jep.2024.118760. Epub 2024 Aug 30.
Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated.
It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity.
The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells.
The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes.
Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.
民族药理学相关性：黄连解毒汤（HLJDD）是一种古老的中药配方，常用于多种疾病，并且已被证明对葡萄糖和脂质代谢具有药理作用。然而，HLJDD 治疗肥胖症和相关代谢紊乱的确切机制仍需进一步研究。
研究目的：人们认为，促进脂肪细胞产热以提高身体的能量消耗是改善代谢异常和减肥的有效策略。在这项研究中，我们研究了 HLJDD 调节脂肪细胞产热以改善肥胖症能量消耗的能力及其潜在机制。
方法：用高脂肪饮食喂养肥胖小鼠 12 周建立肥胖小鼠模型。所有小鼠分为 NC、HFD、HFD 加低剂量 HLJDD（2.25 g/kg/d）和 HFD 加高剂量 HLJDD（4.5 g/kg/d）组，饲养 4 周。进行体外实验以评估含 5%和 10%HLJDD 的血清对分化的 3T3-L1 细胞和敲低 HDAC3 的 3T3-L1 细胞的影响。
结果：结果表明，HLJDD 治疗可显著改善肥胖小鼠的葡萄糖和胰岛素耐量，降低 WAT 中脂肪细胞的半径，并增加能量消耗。此外，HLJDD 治疗可显著增加 WAT 和 3T3-L1 脂肪细胞中 UCP-1 和 PGC-1α 的水平，同时抑制 HDAC3 水平。重要的是，在 HDAC3 敲低脂肪细胞中，HLJDD 对 PGC-1α 和 UCP-1 的作用被阻断。
结论：因此，这些结果表明 HLJDD 通过抑制 HDAC3 增强脂肪细胞产热并改善能量消耗，从而增加 UCP-1 和 PGC-1α 的表达。这些发现放大了 HLJDD 的作用机制及其治疗肥胖症和相关代谢紊乱的潜力。
