食物成瘾及其神经环路调控机制

Food Addiction and Its Neural Circuitry Regulation Mechanism

食物成瘾是指人们对某些特定食物(高度加工、可口、高热量的食物)的依赖性达到难以控制的程度,并表现出一系列成瘾样的行为学变化,具有强迫性、长期性和反复性的特点。食物成瘾可引起肥胖症,而且是大部分人不能维持减肥效果或坚持限制性饮食以保持健康体重的核心因素。深入理解食物成瘾及其神经生物学机制,将为干预食物成瘾以改善肥胖提供准确的靶点。食物成瘾的诊断标准是耶鲁大学食物成瘾量表,而食物成瘾的动物模型为小鼠食物自我管理模型。外侧下丘脑-腹侧被盖区-伏隔核神经环路、腹侧被盖区-前边缘皮质-伏隔核神经环路和外侧隔核-结节核神经环路是调控食物成瘾的关键神经环路机制。

Food addiction refers to the individual dependence on certain specific foods(high-calorie foods)to the extent that it becomes difficult to control and manifests a series of addictive-like behavioral changes.Food addiction is an important factor in the development of human obesity and is also a core factor that most people cannot maintain weight loss or adhere to restrictive diets to maintain a healthy weight.A deeper understanding of food addiction and its neurobiological mechanisms will provide accurate targets for intervening in food addiction to improve obesity.Food addiction is characterized by compulsive,chronic and repetitive nature.The Yale Food Addiction Scale(YFAS),a scale specifically designed to assess food addiction,was developed in 2009 by modeling all the DSM-IV for substance dependence to be applicable to eating behavior.In 2016,Gearhardt developed the Yale Food Addiction Scale 2.0,which contains 35 survey questions,to align the YFAS scale with the diagnostic criteria for addictive disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders.One of the most valid and used animal models for food addiction is the mouse food selfadministration model.The mouse food self-administration model was modified according to the rat cocaine addiction model,and the food addiction status of the animals was evaluated based on three behaviors:persistence of feeding response,feeding motivation,and compulsive feeding.Studies have shown that the neural circuits of the lateral hypothalamus-ventral tegmental area-nucleus accumbens and ventral tegmental area-prelimbic-nucleus accumbens are key neurobiological mechanisms that regulate food addiction.Dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens(NAc)to facilitate food reinforcement,food reward,and food addiction.The corticotropin-releasing factor(CRF)secreted by the hypothalamus may mediate chronic stressinduced VTA-nucleus accumbens reward system dysfunction and promote food addiction in mice.Meanwhile,the nucleus accumbens receives glutamatergic projections from the prelimbic cortex,an integral part of the reward system.Specific inhibition of the PL-NAc neural circuit develops a food addiction-susceptible phenotype in mice.Furthermore,dopaminergic projections from the ventral tegmental area to the prelimbic cortex specifically inhibited the PL-NAc neural circuit to promote a food-addicted phenotype in mice.Additionally,neurotensinpositive neurons in the lateral septum(LSNts)project to the tuberal nucleus(TU)via GABA signaling to suppress hedonic feeding.