肥胖大鼠模型中对食物刺激反应的差异：脑葡萄糖代谢的体内评估
Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism.
作者信息
Thanos P K, Michaelides M, Gispert J-D, Pascau J, Soto-Montenegro M L, Desco M, Wang R, Wang G-J, Volkow N D
机构信息
Department of Medicine, Behavioral Neuropharmacology and Neuroimaging Laboratory, Brookhaven National Laboratory, Upton, NY, USA.
出版信息
Int J Obes (Lond). 2008 Jul;32(7):1171-9. doi: 10.1038/ijo.2008.50. Epub 2008 May 13.
OBJECTIVE
Food intake is regulated by factors that modulate caloric requirements as well as food's reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity.
METHODS
Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using micro-positron emission tomography and 2-[(18)F]-fluoro-2-deoxy-D-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS).
RESULTS
FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus.
CONCLUSIONS
The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal cortex), which corroborates their relevance in the perception of food.
目的
食物摄入受多种因素调节，这些因素既能调节热量需求，又能影响食物的强化特性。在本研究中，我们测量了大脑对嗅觉刺激（培根香味）的葡萄糖利用率，并研究了食物限制和肥胖遗传易感性对这种大脑代谢活动的作用。
方法
将 Zucker 肥胖（Ob）大鼠和瘦（Le）大鼠分为四组：（1）Ob 组自由进食，（2）Ob 组食物限制（自由进食量的 70%），（3）Le 组自由进食，（4）Le 组食物限制。在两种条件下使用微型正电子发射断层扫描和 2-[(18)F]-氟-2-脱氧-D-葡萄糖对大鼠进行扫描：（1）基线扫描（无刺激）和（2）激发扫描（食物刺激，FS）。
结果
FS 导致左右海马体失活。Ob 大鼠与 Le 大鼠相比，FS 引起的变化更大（海马体失活和内侧丘脑激活），且 Ob 组动物而非 Le 组动物使额叶皮质失活并激活上丘。获取食物导致嗅觉核中对食物刺激的代谢变化模式相反（在无限制时失活，在限制时激活），以及右侧岛叶/顶叶皮质中代谢变化模式相反（在无限制时激活，在限制时失活）。此外，限制进食而非自由进食的动物激活了内侧丘脑。
结论
Ob 大鼠中更大的变化表明瘦素调节大脑对熟悉食物刺激的区域反应。同样，食物限制时反应模式的差异表明 FS 受食物获取条件的影响。FS 引起的主要变化发生在海马体（一个与记忆有关的区域）、岛叶皮质（一个与内感受[内部感觉的感知]有关的区域）、内侧丘脑（一个与警觉有关的区域）以及与感觉感知有关区域（嗅球、嗅觉核、枕叶皮质、上丘和顶叶皮质），这证实了它们在食物感知中的相关性。
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