重磅：Cell刊发哥大科研新突破，锁定代谢障碍治疗核心靶点

Core Insights - The article emphasizes the role of the bed nucleus of the stria terminalis (BNST) as a central hub in the brain that regulates feeding behavior by integrating sensory inputs and internal states, providing a unified command for eating actions [17]. Summary by Sections Taste System and Feeding Behavior - The taste system acts as the primary sensory gateway for regulating eating behavior, with specialized taste receptor cells (TRC) identifying taste signals and transmitting information to the taste cortex [7]. - The brain's mechanism for converting sweet taste signals into actual eating behavior remains incompletely understood, despite advancements in sensory biology [7]. Brain Circuitry and Hunger Regulation - Research has identified complex neural networks, including AGRP and POMC neurons, that regulate hunger and feeding, suggesting a universal "feeding control center" in the brain [8]. - The BNST has been identified as a key brain region that integrates internal states and sensory signals, playing a crucial role in the unified regulation of feeding behavior [8]. Neuronal Response to Sweetness - Neurons in the central amygdala (CEA) that respond to sweetness have been characterized, with over 90% of sweet-responsive neurons co-expressing preproenkephalin (Pdyn) [9]. - Activation of Pdyn neurons in the CEA can make mice perceive regular water as an attractive stimulus, while inhibiting these neurons eliminates their preference for sweet substances [9]. BNST's Role in Feeding Response - The CEA-Pdyn neuron pathway projects densely to the BNST, which is critical for mediating sweet-induced feeding responses [10]. - Hunger increases sweet consumption by 2.5 times in mice, with BNST activity enhancing the response to sweetness during hunger [10]. Integration of Signals in BNST - The BNST receives projections from both sweet-responsive neurons in the CEA and hunger-signaling AGRP neurons, allowing it to enhance responses to sweetness and regulate feeding behavior [11]. - In sodium deficiency, BNST's response to salty stimuli increases by 300%, demonstrating its role in integrating various signals for precise feeding regulation [11]. Neuronal Activity and Internal States - BNST neurons can distinguish between different "stimulus-internal state" combinations, with a prediction accuracy of 80% for these combinations [12]. - The number of sweet-responsive neurons in the BNST increases by 40% during hunger, indicating a dynamic response to internal states [12]. Comprehensive Control of Feeding Behavior - Activation of the BNST leads to increased feeding impulses, even for normally avoided substances, while inhibition reduces food intake regardless of hunger or sodium deficiency [14]. - The BNST's ability to control various feeding behaviors suggests it is not limited to specific food types but serves as a general feeding control center [14]. Bidirectional Weight Regulation - The BNST has been shown to regulate body weight in both cachexia and obesity models, with selective activation delaying weight loss by 30% and inhibition leading to an 8% weight reduction comparable to GLP-1 receptor agonists [15][16]. - These findings indicate that the BNST is a potential target for interventions in weight management, particularly in addressing both obesity and cachexia [16]. Conclusion - The BNST is confirmed as the central command center for feeding behavior, integrating sensory inputs and internal states to flexibly adjust feeding preferences and intake [17]. - This discovery provides new insights into the mechanisms of appetite regulation and potential therapeutic targets for obesity and related disorders [17].