以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 深度分享内分泌用药经验、病例剖析、指南专业解读并紧跟国内外内分泌领域前沿进展，「每医健」旗下内容平台。 最新统计数据显示，中国超重和肥胖人群已突破总人口的49%大关。虽然我国肥胖率并非全球最高，但庞大的人口基数使得中国已然成 为世界肥胖人口第一大国。这一严峻形势迫切需要科学界揭示肥胖发生的深层机制。 作为细胞能量工厂的线粒体，其功能异常已被证实与肥胖、胰岛素抵抗及脂肪肝等代谢疾病密切相关。加州大学圣地亚哥分校Al a n R. Sa lti e l教授团队在Na t u r e Me t a bolism发表突破性研究成果，首次阐明高脂饮食会引发白色脂肪细胞内线粒体结构崩解，导致其代谢功 能严重受损。这种线粒体碎片化现象直接阻碍能量消耗，促使脂肪异常蓄积，最终形成恶性循环的肥胖病理过程。 研究团队进一步锁定Ra lA基因为这一过程的关键调控因子。通过基因编辑技术特异性敲除Ra lA基因后，即使持续给予高脂肪饮食，实 验对象仍能维持线粒体完整结构，有效避免体重异常增加。这一发现不仅揭示了肥胖发生的新机制，更为开发靶向Ra lA的减肥疗法提 供了理 ...

Core Viewpoint - The article discusses a groundbreaking study revealing the role of the RalA gene in obesity, particularly how it regulates mitochondrial function and energy metabolism, providing a potential new target for obesity treatment [5][12]. Group 1: Obesity Statistics and Mechanisms - Recent statistics indicate that over 49% of China's population is overweight or obese, making it the country with the highest number of obese individuals globally [4]. - Mitochondrial dysfunction has been linked to metabolic diseases such as obesity, insulin resistance, and fatty liver disease [5]. Group 2: RalA Gene and Obesity - The study identifies RalA as a key regulatory factor in the obesity process, with its expression significantly increased in white adipose tissue (WAT) of mice fed a high-fat diet (HFD) [7]. - RalA knockout mice (RalA-AKO) showed significantly reduced weight gain and improved glucose tolerance when subjected to HFD, indicating that RalA plays a crucial role in high-fat diet-induced obesity [7][8]. Group 3: Impact on Liver and Metabolism - RalA deficiency in mice led to reduced liver fat accumulation and improved glucose and lipid metabolism, suggesting a protective effect against metabolic disorders associated with obesity [8]. - Key metabolic indicators such as liver weight and triglyceride levels were significantly lower in RalA-AKO mice, highlighting the gene's role in metabolic regulation [8]. Group 4: Energy Consumption and Mitochondrial Function - RalA-AKO mice exhibited increased energy expenditure and oxygen consumption without changes in food intake or activity levels, suggesting enhanced mitochondrial function [10]. - The study found that RalA deficiency preserved mitochondrial integrity and function, preventing the fragmentation typically seen in HFD-fed mice [11]. Group 5: Molecular Mechanisms - RalA was shown to regulate mitochondrial dynamics by affecting the phosphorylation of Drp1, a key protein involved in mitochondrial fission, thereby influencing energy metabolism [11][12]. - The research establishes a RalA-Drp1 signaling axis that could be targeted for developing new obesity treatments, emphasizing the potential for therapeutic interventions aimed at this pathway [12][13].