Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism
Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism
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DOI：
10.1093/jn/134.3.648
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发表时间：
2004-03-01
影响因子：
4.2
通讯作者：
Plagemann, A
中科院分区：
文献类型：
--
作者：
Fahrenkrog, S;Harder, T;Plagemann, A
暴露于母亲妊娠糖尿病（GD）“程序”的后代肥胖在童年和以后的生活。最近的临床数据表明，新生儿摄入母乳的糖尿病母亲可能是至关重要的参与。下丘脑基底内侧核团如腹内侧核（VMN）、室旁核（PVN）和弓状核（ARC）在中枢神经系统调节摄食和体重中起关键作用。在ARC中，表达食欲神经肽如神经肽Y（NPY）、甘丙肽（GAL）和刺鼠相关肽（AGRP）以及食欲神经肽如阿黑皮素原（POMC）和α-黑素细胞刺激激素（MSH）。我们研究了新生儿暴露于GD大鼠母奶对断奶大鼠下丘脑核团发育的影响。与GD大鼠母鼠（CO-GD）交叉培养的对照（CO）大鼠母鼠的后代出现出生后早期生长延迟。在出生后第21天，CO-GD大鼠表现出结构和功能性下丘脑“编程障碍”。“CO-GD大鼠的ARC在基础条件下显示NPY和AGRP的免疫阳性增加，尽管葡萄糖，瘦素和胰岛素水平正常。相反，CO-GD大鼠表现出降低免疫阳性的POMC和MSH和免疫阳性神经元的密度降低，与对照大鼠母代交叉培养的对照大鼠母代相比。在VMN中没有发现形态学改变，而CO-GD大鼠显示PVN中神经元总数增加。总之，新生儿通过摄入母鼠乳汁暴露于母体糖尿病导致下丘脑食欲和食欲回路复杂的编程障碍，这些回路关键性地参与食物摄入、体重和代谢的终身调节。
Exposure to maternal gestational diabetes (GD) "programs" offspring for obesity in childhood and later life. Recent clinical data suggest that neonatal ingestion of breast milk from diabetic mothers might be crucially involved. Mediobasal hypothalamic nuclei such as the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the arcuate nucleus (ARC) play a key role in the central nervous system regulation of food intake and body weight. In the ARC, orexigenic neuropeptides such as neuropeptide Y (NPY), galanin (GAL), and agouti-related peptide (AGRP) and anorexigenic neuropeptides such as proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH) are expressed. We investigated the effects of neonatal exposure to milk from GD rat dams on the development of hypothalamic nuclei in weanling rats. Offspring of control (CO) rat dams cross-fostered to GD rat dams (CO-GD) developed early postnatal growth delay. On d 21 of life, CO-GD rats showed structural and functional hypothalamic "malprogramming." The ARC of CO-GD rats showed increased immunopositivity of both NPY and AGRP under basal conditions, despite normal levels of glucose, leptin, and insulin. Conversely, CO-GD rats showed decreased immunopositivity of both POMC and MSH and decreased density of immunopositive neurons, compared with offspring of control rat dams cross-fostered to control rat dams. No morphometric alterations were found in the VMN, whereas CO-GD rats showed an increased total number of neurons in the PVN. In summary, neonatal exposure to maternal diabetes through the intake of dam's milk in rats leads to a complex malprogramming of hypothalamic orexigenic and anorexigenic circuits that are critically involved in the lifelong regulation of food intake, body weight, and metabolism.