以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 你有没有注意到，冬天似乎更容易变瘦，而到了夏天体重却容易增加？其实，这种现象并非你的错觉！近期，丹麦哥本哈根大学联合瑞典卡罗 林斯卡学院的研究团队发现，季节性的光照时长变化会通过调控进食规律，从而影响人体的能量代谢与脂肪储存。 这项刊登在《Cell Metabolism》的最新成果，让我们看到了无需节食或锻炼也能瘦身的"天然减重新思路"。 一、光照如何成为"隐形减脂教练" 短日照：激活身体的"燃脂开关" 二、科学实证：光照减脂的三大核心机制 外周生物钟：光照"重置"代谢节奏 通过RNA测序和qPCR分析，科学家们发现短日照改变了肝脏、肌肉等外周组织的核心生物钟基因节律。例如，肝脏中脂质代谢相关基因的节 律高峰，在短日照条件下会延后约4小时，这种相位变化直接影响脂肪的合成与分解。 呼吸代谢：短日照提升脂肪燃烧效率 在实验中，科学家们将小鼠分为三组，分别模拟夏季 ...

以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 减肥道理人人都懂，"少吃多动"四字真言简单明了。然而实践起来却难如登天，改变生活方式需要决心、毅力、时间、金钱缺一不可。至于那 些激进医疗手段，多数人又没到非用不可的地步，吃药手术既花钱又伤身。 有没有谁能替我吃掉那些热量，让我不费力就变瘦呢？（做梦谁不会呀） 别笑，这还真不是痴人说梦！近期《细胞·代谢》杂志刊登了日本RIKEN研究所科研团队的一项突破性研究，提出了一种借助肠道菌群"代 吃"的减重创新思路。 研究人员发现，乙酰纤维素(AceCel)能有效重塑肠道菌群组成与功能，特别是显著增强了肠道多形拟杆菌(Bacteroides thetaiotaomicron)的碳 水化合物代谢能力，大量消耗原本会被人体吸收的单糖。 用大白话说就是：乙酰纤维素能召唤特定肠道细菌充当"碳水清道夫"，替你吃掉部分碳水化合物，让身体少吸收热量，自然而然地瘦下来。 虽然研究聚焦 ...

整理 | GLP1减重宝典内容团队 1月7日，上海世领制药宣布，其研发的全球首款GLP-1经黏膜递送制剂正式获得美国FDA临床试验批准。这标志着GLP-1药物从"疗效 竞争"向"用药体验竞争"迈出关键一步。 根据相关专利和研究，该鼻喷剂采用纳米喷雾设计（微细粒子<5μm占比≥30%）和辛酸钠等吸收促进剂，可通过鼻腔黏膜直接吸收，使 生物利用度提升至37.1%-52.1%，接近注射剂水平。此外，鼻腔给药可直接穿透血脑屏障，为未来开发针对食欲调节中枢的新适应症 （如暴食症或代谢综合征）提供可能。 国外也有类似探索。瑞典Orexo公司近期在《Nature》子刊报道，其基于AmorphOX无定形纳米技术的司美格鲁肽粉末型鼻腔制剂，在 比格犬模型中实现41%的肺部沉积率（传统鼻喷剂仅15%-20%），血浆峰浓度达注射剂的89%，半衰期延长至180小时，几乎与原研注 射剂相当。 市场格局或将迎来新变化 上海世领的鼻喷剂临床申请受理，标志着GLP-1药物剂型创新进入新阶段。未来，它有望成为继注射剂和口服制剂后的第三大主流剂 型。随着更多临床数据公布，司美格鲁肽市场可能从原研药单一主导，转向"剂型创新+仿制竞争+市场分层"的 ...

Core Viewpoint - GLP-1 receptor agonists, particularly Tirzepatide and Semaglutide, show significant weight loss effects, but the importance of resistance training alongside aerobic exercise is often overlooked, leading to potential muscle loss and metabolic decline [2][6][8]. Group 1: Drug Mechanism and Weight Loss - Tirzepatide demonstrates a dual-target mechanism by activating both GLP-1 and GIP receptors, resulting in an average weight loss of 22.5% (24 kg) over 72 weeks, while also improving metabolic issues like fatty liver and insulin resistance [6]. - The combination of resistance training and aerobic exercise has been shown to outperform the use of Tirzepatide alone in improving cardiovascular function and muscle strength [4]. Group 2: Importance of Resistance Training - Resistance training is crucial for maintaining muscle mass and metabolic rate during weight loss, as muscle tissue burns approximately 13 kcal per kg daily [7][10]. - Clinical cases indicate that individuals relying solely on aerobic exercise may experience muscle loss and decreased metabolic rate, emphasizing the need for a balanced exercise regimen [12]. Group 3: Metabolic Adaptation and Weight Regain - Users of GLP-1 medications may face a 10% decrease in basal metabolic rate after discontinuation if muscle mass is not preserved through exercise, increasing the risk of weight regain [8]. - The American College of Sports Medicine (ACSM) stresses the necessity of combining medication with exercise to avoid adverse health effects from weight loss [8]. Group 4: Recommended Exercise Protocols - ACSM recommends a combination of moderate aerobic and resistance training, suggesting 3-4 sessions of low to moderate intensity aerobic exercise per week, alongside 2-3 sessions of resistance training [15]. - Individualized adjustments in exercise intensity and frequency are essential to prevent excessive energy expenditure and potential adverse effects [16]. Group 5: Nutritional Considerations - Users of GLP-1 medications should consume 1.6-2.2 grams of protein per kg of body weight daily to support muscle synthesis, with a focus on high-protein meals to minimize muscle breakdown [19]. - A higher protein intake has been associated with less loss of lean body mass during weight loss compared to lower protein diets [19]. Group 6: Conclusion - The integration of GLP-1 medications with a scientifically designed exercise and nutrition plan is vital for effective weight management, aiming for sustainable health outcomes without adverse effects [20].

Core Viewpoint - The article discusses the planned price increases of prescription drugs by U.S. pharmaceutical companies in 2026, despite ongoing pressure from the Trump administration to lower drug prices. The number of drugs set for price increases has risen compared to the previous year, indicating a persistent issue with high drug costs in the U.S. [5][7] Price Increases - U.S. pharmaceutical companies plan to raise prices on at least 350 prescription drugs in 2026, including vaccines for COVID-19, respiratory syncytial virus (RSV), and shingles, as well as the cancer drug Ibrance [5] - The median price increase for these drugs is approximately 4%, consistent with the increase seen in 2025 [5] - In contrast, around 9 drugs will see price reductions, with the diabetes drug Jardiance and its related medications experiencing a price drop of over 40% [5] Comparison with Other Countries - Patients in the U.S. pay significantly higher prescription drug costs compared to other developed countries, often nearly three times as much [7] - Despite agreements reached by Trump with 14 pharmaceutical companies to lower some drug prices, companies still plan to increase prices starting January 1 [7] Specific Company Actions - Pfizer plans to adjust prices for about 80 drugs, including Ibrance, Nurtec, and Paxlovid, with most increases below 10%. However, the price of the COVID-19 vaccine Comirnaty will rise by 15%, and some hospital drugs will see increases exceeding four times their previous prices [7] - European pharmaceutical company GSK intends to raise prices on approximately 20 drugs and vaccines, with increases ranging from 2% to 8.9% [8] Legislative and Market Context - U.S. pharmaceutical companies have been reducing significant price hikes in recent years due to legislative scrutiny and government policies that penalize drug prices exceeding inflation rates [8] - More price adjustments are expected to be announced in early January, a traditional peak period for pharmaceutical price changes [8]

Core Viewpoint - The article focuses on individuals who successfully lose weight through lifestyle changes but experience weight regain, highlighting the challenges of long-term obesity management and effective strategies to prevent weight rebound [7][11]. Summary by Sections Weight Rebound Challenges - A systematic review and meta-analysis indicate that approximately 75% of individuals who lose an average of 14 kg through lifestyle interventions will regain weight within about five years [7]. - Weight rebound is not limited to those who undergo lifestyle changes; individuals who stop medication or have undergone weight loss surgery also face similar challenges [7]. Mechanisms Behind Weight Rebound - Research from 2022 shows that macrophages in adipose tissue produce elevated levels of lipopolysaccharide-induced cytokines, contributing to a "fat memory" that increases the risk of weight regain [9]. - A 2023 study published in *Nature Metabolism* reveals that obese individuals have a diminished brain response to nutritional stimuli, which may be a key factor in weight rebound after successful weight loss [9]. Strategies to Reduce Weight Rebound Risk 1. **Dietary Adjustments** - High-protein, low glycemic index (GI), or low glycemic load diets can help reduce the risk of weight rebound. Anti-inflammatory dietary patterns are also recommended [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, and promotes fat oxidation, which aids in maintaining weight loss [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are suggested to prevent weight rebound by reducing adipose tissue mass [13]. 4. **Individualized Management and Ongoing Research** - The occurrence of weight rebound is influenced by multiple factors, necessitating further scientific research to explore more effective long-term management strategies [14].

Core Viewpoint - The article discusses the rising global obesity rates and highlights the potential of cysteine-restricted diets as an intervention method, focusing on the molecular mechanisms behind rapid weight loss induced by cysteine limitation [8][9]. Research Background and Purpose - Background: The global obesity prevalence is increasing, and cysteine-restricted diets are gaining attention as a potential intervention method. Cysteine is a crucial precursor for synthesizing glutathione (GSH) and coenzyme A (CoA), but the specific effects of cysteine limitation on body weight and its regulatory mechanisms remain unclear [8]. - Purpose: The study aims to explore the molecular mechanisms behind rapid weight loss induced by cysteine restriction using mouse experiments, providing new targets for obesity treatment [9]. Research Methods - Study Design: The research utilized Cse gene knockout (KO) and wild-type (WT) mice, administering cysteine-restricted diets (no-Cys) and other essential amino acid-restricted diets, combined with metabolic cage monitoring and comprehensive transcriptomic and metabolomic analyses [10]. - Data Sources: The study collected metabolic products from mouse liver, muscle, fat tissues, serum, and urine, with sample sizes ranging from 3 to 9 mice per experimental group [11]. - Research Variables: The focus was on cysteine intake, body weight changes, and metabolic indicators such as GSH, CoA, and inflammatory factors [12]. - Analysis Methods: Techniques included RNA sequencing, LC-MS metabolomics, immunohistochemistry, Western blotting, and indirect energy metabolism measurement [13]. Research Results 1. Cysteine deficiency leads to rapid and reversible weight loss: Cse KO mice on a no-Cys diet experienced a weight loss of up to 30% within one week, significantly exceeding other essential amino acid-restricted groups. Weight returned to baseline upon resuming normal diet, indicating that weight loss was primarily due to cysteine deficiency [14]. 2. Metabolic reprogramming promotes fat consumption and browning: The no-Cys diet reduced the respiratory exchange ratio (RER) and total fat mass, with a notable increase in UCP1-positive cells in white adipose tissue, indicating brown fat characteristics. Liver transcriptomic results showed activation of fatty acid oxidation pathways and suppression of fat synthesis genes [16]. 3. Integration of stress pathways and oxidative stress: Cysteine restriction activated integrated stress response (ISR) and oxidative stress response (OSR), significantly increasing serum levels of GDF15 and FGF21. Deletion of Gdf15 or Fgf21 slowed weight loss, suggesting their roles in metabolic adaptation regulation [19]. 4. CoA reduction leads to decreased metabolic efficiency: The no-Cys diet lowered liver CoA levels, resulting in increased urinary excretion of TCA cycle intermediates, indicating impaired mitochondrial oxidative phosphorylation capacity [20][21]. 5. Tissue-specific regulation of energy metabolism pathways: ISR and OSR-related genes were significantly upregulated in the liver, while muscle primarily activated oxidative stress pathways, and adipose tissue emphasized lipolysis and browning responses, demonstrating coordinated regulation across multiple tissues for systemic metabolic remodeling [23]. Research Conclusion and Limitations - Conclusion: Cysteine restriction promotes rapid weight loss by depleting GSH and CoA, activating stress responses, enhancing fat oxidation, reducing metabolic efficiency, and stimulating creatine cycling compensation. This physiological process is reversible and offers new insights for obesity treatment [27]. - Limitations: The study has not assessed the safety of cysteine restriction in humans, and the long-term effects on other organs and gender differences remain unexplored, necessitating further validation of the underlying mechanisms [28]. Future Research Directions - Future studies should evaluate the weight loss effects and safety of cysteine restriction in primates, analyze the impact of cysteine deficiency on gut microbiota, and explore the molecular mechanisms of gender differences in response to cysteine restriction to advance personalized intervention strategies [29].

Core Viewpoint - Arrowhead Pharmaceuticals is targeting the obesity market with two gene-silencing candidates showing potential for fat reduction rather than just weight loss, leading to a significant stock price increase after the announcement [5][8]. Group 1: Clinical Data and Mechanisms - Arrowhead disclosed early clinical data for two assets with different mechanisms: one targeting liver INHBE gene expression and the other targeting ACVR1C gene in adipocytes [5]. - In a small exploratory study, participants with obesity and type 2 diabetes showed an average weight loss of 9.4% after 16 weeks of treatment with ARO-INHBE combined with tirzepatide, compared to 4.8% in the control group using tirzepatide plus placebo [6]. - The combination therapy also resulted in reductions in visceral fat, total fat, and liver fat content, although Arrowhead did not disclose data on ARO-INHBE as a monotherapy [6][8]. Group 2: Industry Insights and Regulatory Changes - The industry consensus suggests that such molecules are more likely to serve as enhancers of GLP-1 drugs rather than standalone weight loss medications [7]. - Regulatory pathways are evolving, with the FDA potentially accepting "additional quantifiable fat reduction effects on top of GLP-1" as a primary endpoint, shifting focus from mere weight loss to fat distribution and muscle preservation [7]. - Arrowhead's ACVR1C-targeting asset, ARO-ALK7, showed an 88% average reduction in ALK7 mRNA in adipose tissue at a 200 mg dose, with a 14.1% average reduction in visceral fat after 8 weeks [7]. Group 3: Market Reaction and Future Outlook - The market reacted positively, with Arrowhead's stock rising approximately 17% to $75, indicating investor confidence in the potential of next-generation obesity treatments that may focus on deeper metabolic regulation rather than solely on incretin-based therapies [8].

Core Viewpoint - The article discusses the safety and efficacy of GLP-1 receptor agonists (GLP-1RA) in treating type 2 diabetes and obesity, highlighting their common side effects and contraindications, as well as the ongoing debate regarding their association with thyroid cancer risk [4][10][14]. Group 1: Safety and Side Effects - Common side effects of GLP-1RA include nausea, diarrhea, vomiting, constipation, abdominal pain, and gastroesophageal reflux disease, which tend to alleviate over time [4]. - Semaglutide shows good safety in diabetes treatment but can cause gastrointestinal issues, with 17% of patients reporting nausea even at low doses (0.5 mg), and higher rates of diarrhea (12.2%) and vomiting (6.4%) as doses increase [5]. - Approximately 80% of tirzepatide users report at least one side effect, with nausea (33%) and diarrhea (23%) being common, similar to semaglutide [7]. Group 2: Contraindications and Warnings - GLP-1RA medications carry a black box warning for potential increased risk of thyroid C-cell tumors, advising against use in patients with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 [10][11]. - Other warnings include risks of pancreatitis, hypoglycemia when used with certain diabetes medications, and potential kidney damage [10]. - Patients with a history of pancreatitis, severe gastrointestinal diseases, or those under 18 years old should use GLP-1RA cautiously [12]. Group 3: Thyroid Cancer Risk - Animal studies suggest a link between GLP-1RA and the development of medullary thyroid carcinoma (MTC), leading to black box warnings for at-risk patients [14]. - The European Medicines Agency (EMA) has evaluated the risk, concluding that current evidence does not support a causal relationship between GLP-1RA and thyroid cancer, despite some observational studies indicating increased risk [16][17].

Core Viewpoint - The article highlights the significant potential of AI in the weight loss industry, exemplified by the success of Simple Life, which has achieved substantial revenue growth and innovative engagement strategies in its offerings [2][11]. Group 1: Company Overview - Simple Life, based in London, recently completed a financing round of $35 million (approximately 250 million RMB) and reported an annual revenue of $100 million (approximately 700 million RMB), with a year-on-year growth of 64% [2]. - The company integrates scientific weight loss methods with AI, transforming the weight loss process into a gamified experience [5][11]. Group 2: Product Features - Simple Life's product includes a success points system that calculates "success scores" based on user behavior, allowing users to track their weight loss progress in a game-like manner [7]. - The platform offers gamified incentives, rewarding users for completing weight loss tasks with tangible rewards or virtual honors [7]. - An AI coach named Avo provides personalized advice on nutrition, exercise, and lifestyle adjustments, processing around 300,000 dietary records daily and conducting over 100,000 guidance conversations [9]. Group 3: Market Analysis - Despite the lucrative potential of AI in weight loss, there are few domestic competitors in China, with only a handful of companies receiving venture capital support in the past three years [13][14]. - The domestic weight management market is projected to reach 326 billion RMB by 2025, indicating a strong demand for effective weight loss solutions [16]. - The article suggests that the success of Simple Life in international markets signals a clear market demand, with over 500 million people in China classified as overweight or obese [15]. Group 4: Future Outlook - The article posits that the domestic AI weight loss market may see the emergence of new unicorn companies in the next three years, driven by the growing demand for innovative weight management solutions [17].