亮氨酸对正常人及2型糖尿病患者摄食奖赏中枢作用的静息态功能磁共振研究

The effect of leucine on feeding center and reward system in T2DM patients and healthy control subjects: a resting-state fMRI study

目的采用静息态功能磁共振研究2型糖尿病(type 2 diabetes mellitus,T2DM)患者口服亮氨酸后摄食奖赏中枢的功能连接改变,并分析其与T2DM相关代谢指标的关系。材料与方法共招募17名受试者,正常组8名,T2DM组9例,利用血氧水平依赖信号(blood oxygen level dependent,BOLD)序列采集数据,选取摄食奖赏相关脑区作为种子点,计算在口服亮氨酸前后其与全脑其他体素间的功能连接值,并分析两组间存在显著组间差异的连接值与临床指标间的相关性。结果正常组口服亮氨酸后,右侧小脑后叶与左侧眶额皮层间的功能连接强度增加(P<0.05);双侧前额叶皮层、眶额叶皮层、前扣带回、边缘叶与左侧壳核连接强度增加(P<0.05),而T2DM组口服亮氨酸后相应脑区功能连接强度没有显著增加(P>0.05),相关性分析结果显示部分脑功能功能连接强度改变与T2DM组空腹胰岛素水平及HOMA2-IR呈负相关(P<0.05),与正常组血浆亮氨酸水平呈正相关(P<0.05)。结论 T2DM损害了奖赏摄食相关脑区的功能连接,左侧眶额皮层与右侧小脑后叶之间的连接强度与胰岛素抵抗程度相关,中枢胰岛素抵抗可能损害了亮氨酸感知通路。

Objective:To study the functional connectivity of the reward system and feeding center after oral leucine in type 2 diabetes mellitus by resting-state fMRI,and analyze the relationships between the changes and related metabolic indicators of T2DM during this test.Materials and Methods:This study included several T2DM patients(T2DM,n=9)whose age,sex,education match up with healthy control subjects(HC,n=8).Resting-state fMRI data were collected by blood oxygen level dependent sequence(BOLD).Brain regions involving in feeding center and reward system were selected as seeds,and functional connection values between these seeds and other voxels in the brain were calculated after oral leucine,the resulted values of both groups were compared using two-sample t-test to locate the regions with significant change.Then correlation analysis was conducted between clinical indexes and values of functional connection extracted from significant difference between groups.Results:After oral leucine,HC group people showed significantly increased functional connectivity between left orbitofrontal cortex and right cerebellum posterior lobe(P<0.05).The functional connection values between the prefrontal cortex,the anterior cingulum cortex,orbitofrontal cortex,limbic lobe and left putamen increased significantly(P<0.05),however there were no significant differences in T2DM group(P>0.05).Moreover,negative correlations were found between the changes of functional connection values of brain function and fasting serum insulin,HOMA2-IR in T2DM group(P<0.05).Positively correlations were found between the changes of functional connection values of brain function and plasma leucine level in HC group(P<0.05).Conclusions:T2DM damage the functional connectivity of reward-associated brain regions,and the functional connectivity between left OFC and cerebellar tonsils was correlates with the degree of HOMA2-IR and fasting serum insulin.Moreover,this study indicated that central insulin resistance may damage the leucine sensing pathway.