Annals of the New York Academy of Sciences Brain Orexin Promotes Obesity Resistance
Annals of the New York Academy of Sciences Brain Orexin Promotes Obesity Resistance
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通讯作者：
A. N. Acad;Sci;C. Kotz;J. Nixon;T. Butterick;C. Perez-Leighton;J. Teske;C. Billington
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作者：
A. N. Acad;Sci;C. Kotz;J. Nixon;T. Butterick;C. Perez-Leighton;J. Teske;C. Billington
对肥胖的抵抗力正在成为一种例外而不是常态，如果我们要找到扭转这一趋势的新方法，了解导致一些人在肥胖环境中保持苗条的机制至关重要。能量摄入和身体活动水平都有助于体重管理，但对大多数人来说，要在这两个因素中做出重大的长期改变是具有挑战性的。正式锻炼之外的身体活动，也称为日常生活活动，严格来说，自发身体活动（SPA），可能是预防肥胖的一个有吸引力的可修改变量。在这篇综述中，我们讨论了SPA和NEAT（非运动产热，或SPA消耗的能量）的个体差异及其与肥胖抵抗的关系。下丘脑神经肽食欲素（hypocretin）可能在调节SPA和NEAT中起关键作用。我们讨论了如何提高食欲素信号转导能力，在一个大脑网络的背景下，调制SPA，可能发挥重要作用，在SPA和NEAT定义个体变异。这种SPA网络的更大激活导致脂肪量增加的倾向更低，因此可能是肥胖预防和治疗的有吸引力的靶点。肥胖和个体差异性肥胖是一种由身体脂肪慢性过量1定义的疾病，与预期寿命缩短、代谢综合征、2型糖尿病和冠心病呈正相关。2肥胖已成为一个公共卫生问题，因为在过去二十年中，无论是发达国家还是欠发达国家，成人和儿童的肥胖发生率都有所增加。3-5人类对肥胖的易感性存在很大差异，这是由环境和遗传因素决定的。6-9决定这种变化的一个主要因素是身体活动，特别是被称为非运动诱导产热（NEAT）的总能量消耗的一个组成部分。10-12 NEAT包括所有形式的能量，但根据http：//wiley onlinelibrary.com/onlineopen#OnlineOpen上列出的条款和条件，允许重复使用本品。10，13 -15自发性身体活动（SPA）的补充概念用于描述“不符合自愿锻炼条件的任何类型的身体活动”。“16，17 SPA和NEAT都有遗传成分。17，18 SPA和NEAT是不可互换的，而是互补的概念：NEAT是指能量消耗，而SPA描述了导致NEAT的身体活动类型。…
Resistance to obesity is becoming an exception rather than the norm, and understanding mechanisms that lead some to remain lean in spite of an obesigenic environment is critical if we are to find new ways to reverse this trend. Levels of energy intake and physical activity both contribute to body weight management, but it is challenging for most to adopt major long-term changes in either factor. Physical activity outside of formal exercise, also referred to as activity of daily living, and in stricter form, spontaneous physical activity (SPA), may be an attractive modifiable variable for obesity prevention. In this review, we discuss individual variability in SPA and NEAT (nonexercise thermogenesis, or the energy expended by SPA) and its relationship to obesity resistance. The hypothalamic neuropeptide orexin (hypocretin) may play a key role in regulating SPA and NEAT. We discuss how elevated orexin signaling capacity, in the context of a brain network modulating SPA, may play a major role in defining individual variability in SPA and NEAT. Greater activation of this SPA network leads to a lower propensity for fat mass gain and therefore may be an attractive target for obesity prevention and therapy. Obesity and individual variability Obesity is a condition defined by a chronic excess of body fat 1 and is positively correlated with shorter life expectancy, metabolic syndrome, type 2 diabetes, and coronary heart disease. 2 Obesity has become a public health issue, as its incidence in adults and children has increased in the last two decades across both developed and underdeveloped societies. 3–5 Humans show large variation in their susceptibility to obesity, which is determined by both environmental and genetic factors. 6–9 A major factor in determining this variability is physical activity, and specifically a component of overall energy expenditure known as nonexercise induced thermogenesis (NEAT). 10–12 NEAT includes all forms of energy ex-Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wiley onlinelibrary.com/onlineopen#OnlineOpen Terms penditure not associated with formal exercise, such as standing and fidgeting. 10,13–15 The complementary concept of spontaneous physical activity (SPA) is used to describe " any type of physical activity that does not qualify as voluntary exercise. " 16,17 Both SPA and NEAT have a heredability component. 17,18 SPA and NEAT are not interchangeable but are complementary concepts: NEAT refers to energy expenditure while SPA describes the types of physical activity that result in NEAT. …