陶罗脱氧胆酸可以缓解肥胖引起的内皮功能障碍
Hanlin Lu1, Zhinan Wu1, Meng Wan2
1State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Rd, Jinan 250012, China.
European heart journal
|October 3, 2025
概括
陈氧胆酸 (CDCA) 可以识别肥胖引起的内皮功能障碍 (ED). 陶氏二氧化醇酸 (TCDCA) 显示了ED的治疗潜力,通过TCDCA-FXR-PHB1-ATF4途径促进新陈代谢.
科学领域:
- 心血管研究研究心血管研究
- 代谢学 代谢学 代谢学
- 内分泌学 在内分泌学.
背景情况:
- 肥胖显著增加心血管疾病 (CVD) 的风险,内皮功能障碍 (ED) 是早期的病理变化.
- 了解非高血压肥胖 (NHO) 个体的ED异质性对于有效的预防和治疗策略至关重要.
- 代谢分析可能会揭示与肥胖相关的ED的新生物标志物和治疗点.
研究的目的:
- 在NHO个体中表征ED异质性.
- 调查血清代谢物和肥胖引起的ED之间的关联.
- 为了确定肥胖引起的ED的预测性和治疗性代谢物.
主要方法:
- 在213名NHO患者 (代谢上健康的肥胖[MHO]和代谢上不健康的肥胖[MUO]) 中,导线肌图评估了ex vivo arteriole ED.
- 针对性代谢学分析确定了与ED相关的血清代谢物.
- 机理学研究探讨了TCDCA-FXR-PHB1-ATF4通路在内皮细胞中的作用.
主要成果:
- 在NHO患者中,肥胖引起的ED与传统心血管疾病风险因素的相关性有限.
- MHO和MUO组表现出类似的ED和代谢概况.
- 血清代谢发现了胆酸 (BAs),特别是陈氧胆酸 (CDCA),与ED有负相关性. 陶氏脱氧胆酸 (TCDCA) 保护ED和高血压,通过内皮FXR激活,PHB1和ATF4进行介导,增强血清和单碳代谢.
结论:
- CDCA是识别肥胖引起的ED的潜在生物标志物.
- 对于各种形式的肥胖引起的ED,TCDCA显示出治疗潜力.
- TCDCA-FXR-PHB1-ATF4轴通过调节新陈代谢提供了一种新的策略,可以通过调节新陈代谢来延迟高血压和心血管疾病的发病.
相关概念视频
Atherosclerosis III: Management
319
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
319
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
166
Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
166
Pharmacokinetics in Obese Patients: Drug Absorption and Distribution
246
Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
246
Obesity
1.1K
The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...
1.1K
Cholesterol: Significance and Regulation
1.2K
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
1.2K
Drug Dosing: Obese Patients
222
In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
222


