Himms-Hagen J
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Proc Soc Exp Biol Med. 1995 Feb;208(2):159-69. doi: 10.3181/00379727-208-43847a.
The hypothesis proposed in this review provides a novel view of both the control of feeding and the function of brown adipose tissue (BAT) thermogenesis. It takes into account the episodic nature of feeding in rats allowed free access to food and the necessity for episodic events in the controlling systems which govern initiation and termination of feeding. A feeding episode is proposed to occur during an episode of increased sympathetic nervous system activity that stimulates BAT thermogenesis and increases body temperature. Two different aspects of stimulated BAT metabolism, namely increased uptake of glucose and increased heat production, evoke initiation and termination of feeding, respectively. Initiation is mediated by a transient dip in blood glucose concentration caused by stimulated glucose utilization in BAT. Feeding continues while both BAT and core temperature continue to rise. Termination is induced by the high level of core temperature brought about by the episode of stimulated BAT thermogenesis. The time between initiation and termination determines the size of the meal and depends on the balance between BAT thermogenesis and heat loss, and thus on ambient temperature. The underlying cause of the episodic stimulation of sympathetic nervous system activity is a decline in core temperature to a level recognized by the hypothalamus as needing a burst of increased heat production. Thus, BAT thermogenesis is important in control of meal size, relating it to thermoregulatory needs. When this function is lost, as in many obese animal models of obesity, the animal loses its ability to remain in energy balance by precisely adjusting its intake in relation to environmental temperature and meal size increases. The hypothesis also predicts that an increase in endogenous heat production that is not due to BAT thermogenesis will prevent the matching of intake to increased expenditure via thermoregulatory feeding. This is seen, for example, in the shivering rat during the early stage of acclimation to cold. Feeding is viewed as the outcome of a thermoregulatory event. Rats do not eat to warm up; they start to eat after they have started to warm up and stop eating once they have warmed up. The phenomenon is termed thermoregulatory feeding, to distinguish it from feeding initiated by other stimuli.
本综述中提出的假说为进食控制和棕色脂肪组织(BAT)产热功能提供了全新视角。它考虑了自由进食大鼠进食的间歇性本质,以及控制系统中控制进食起始和终止的间歇性事件的必要性。进食发作被认为发生在交感神经系统活动增强的时段,这种增强刺激了BAT产热并升高了体温。刺激的BAT代谢的两个不同方面,即葡萄糖摄取增加和产热增加,分别引发进食的起始和终止。起始由BAT中刺激的葡萄糖利用导致的血糖浓度短暂下降介导。在BAT和核心体温持续上升时进食继续。终止由刺激的BAT产热时段导致的高水平核心体温诱发。起始和终止之间的时间决定了进食量的大小,并取决于BAT产热和热量散失之间的平衡,进而取决于环境温度。交感神经系统活动间歇性刺激的根本原因是核心体温下降到下丘脑认为需要一阵产热增加的水平。因此,BAT产热在进食量控制中很重要,将其与体温调节需求联系起来。当这种功能丧失时,如在许多肥胖动物模型中,动物就失去了通过根据环境温度精确调整摄入量来维持能量平衡的能力,进食量会增加。该假说还预测,非BAT产热引起的内源性产热增加将阻止通过体温调节性进食使摄入量与增加的能量消耗相匹配。例如,在适应寒冷初期的颤抖大鼠中就可见这种情况。进食被视为体温调节事件的结果。大鼠不是为了变暖而进食;它们在开始变暖后才开始进食,一旦变暖就停止进食。这种现象被称为体温调节性进食,以区别于由其他刺激引发的进食。