Core Insights - Obesity has become a global public health issue, with adult overweight rates in China reaching 35% and obesity rates at 14.6%. Traditional methods of "eating less and moving more" have shown limited effectiveness. A groundbreaking study published in *Nature Metabolism* reveals that a deficiency in cysteine can activate fat-burning mechanisms, leading to weight loss of up to 30% in animals within a week and reversing inflammation, presenting a new direction for obesity intervention [6][7]. Group 1: Metabolic Mechanisms - Cysteine is a core raw material for the synthesis of glutathione (GSH) and coenzyme A (CoA). When cysteine is deficient, levels of GSH and CoA decrease, activating integrated stress response (ISR) and oxidative stress response (OSR), which accelerates fat oxidation. Animal experiments show that mice lacking cysteine lost 25-30% of their body weight and significantly reduced fat tissue within a week. However, weight returned upon resuming a normal diet, indicating the reversibility of this process [7]. - The conversion of white fat to thermogenic brown fat is enhanced by increased expression of UCP1 protein. Interestingly, even with the UCP1 gene knocked out, weight loss effects remained significant, suggesting the existence of a thermogenic mechanism independent of UCP1. The activation of the sympathetic nervous system and elevated norepinephrine levels in fat tissue promote fat breakdown through β3 adrenergic receptor signaling [8]. - Mice on a high-fat diet showed significant weight loss and improved blood glucose and insulin sensitivity after cysteine-deficient dietary intervention. Levels of inflammatory factors in fat tissue, such as IL-6 and IL-1β, were significantly reduced. A schematic of the cysteine metabolic pathway indicates that caloric restriction enhances cysteine production pathways while reducing related metabolites from the methionine cycle [9]. Group 2: Future Intervention Strategies - Future strategies may involve simulating the effects of cysteine deficiency to regulate downstream hormones (such as GDF15 and FGF21) or targeting CTH enzyme to avoid oxidative damage caused by direct cysteine restriction. While weight loss drugs like GLP-1 receptor agonists have shown efficacy, the cysteine pathway may represent a more direct target for metabolic regulation in drug development [10].

Core Viewpoint - The article discusses the significant role of cysteine in weight management and metabolic regulation, highlighting recent research that shows cysteine restriction can lead to substantial weight loss and metabolic reprogramming, offering new therapeutic strategies for obesity and related metabolic diseases [6][9]. Summary by Sections Essential Amino Acids and Cysteine - In 1937, William C. Rose established the nine essential amino acids (EAA) necessary for human health, with cysteine becoming essential for organisms with specific gene mutations [6]. - Cysteine is crucial for protein synthesis and is a key component in the antioxidant defense system, particularly in the synthesis of glutathione [7]. Cysteine Restriction and Weight Loss - A study published in Nature revealed that conditional cysteine restriction can lead to a weight loss of up to 30% within one week, surpassing the effects of other essential amino acid restrictions [7][9]. - This weight loss effect is reversible and not influenced by environmental temperature [9]. Mechanisms of Action - Cysteine deficiency activates integrated stress responses and oxidative stress responses, creating a positive feedback loop that enhances the expression of key metabolic regulators like GDF15 and FGF21 [9]. - The study found a significant reduction in tissue coenzyme A (CoA) levels, leading to impaired mitochondrial function and metabolic reprogramming characterized by increased anaerobic glycolysis and TCA cycle dysfunction [9]. Implications for Obesity Treatment - The findings suggest that cysteine metabolism plays a central role in energy balance, providing new insights for addressing the global obesity crisis and related metabolic diseases [9].