Catecholaminergic projections into an interconnected forebrain network control the sensitivity of male rats to diet-induced obesity.
Catecholaminergic projections into an interconnected forebrain network control the sensitivity of male rats to diet-induced obesity.
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儿茶酚胺能投射到相互连接的前脑网络中，控制着雄性大鼠对饮食引起的肥胖的敏感性。
DOI：
10.1152/ajpregu.00423.2017
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Watts,AlanG
中科院分区：
文献类型：
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作者：
Lee,ShinJ;Jokiaho,AnneJ;Sanchez-Watts,Graciela;Watts,AlanG
后脑儿茶酚胺神经元将来自肠道的代谢信号传递给下丘脑和邻近前脑中相互连接的神经元网络。这些神经元对短期血糖控制、糖皮质激素和葡萄糖摄取反应以及胰高血糖素样肽1(GLP-1)信号转导至关重要。在这里，我们研究这些途径是否也有助于通过控制对高脂肪/高蔗糖选择(HFSC)饮食的肥胖敏感性来促进长期能量平衡。我们通过下丘脑室旁核注射抗多巴胺-β-羟基酶结合皂苷(DSAP)的方法消融了雄性大鼠的后脑儿茶酚胺能投射。我们测量了DSAP病变对食物选择、内脏肥胖、血糖、胰岛素和瘦素的影响，以及ACTH和皮质酮长期分泌的指标。我们还确定了损伤对增加内脏脂肪所需的碳水化合物或脂肪卡路里数量的影响。最后，我们检测了PVH和弓状核中促肾上腺皮质激素释放激素的水平，神经肽Y(NPY)、刺鼠相关肽(AgRP)和前阿片黑素皮质素(POMC)的表达。注射DSAP的饲料喂养的大鼠会缓慢增加内脏脂肪，但很快就会出现轻微的胰岛素抵抗和血糖升高。然而，注射DSAP的HFSC喂养的大鼠显著增加了摄食量、体重和内脏脂肪，超过了喂养HFSC的对照大鼠的水平。这些变化伴随着1)产生内脏脂肪所需的碳水化合物卡路里数量的减少，2)Npy、AgRP和Pomc表达的异常，以及3)胰岛素分泌和糖皮质激素负反馈的异常控制。因此，长期适应高碳水化合物饮食的代谢需要完整的前脑儿茶酚胺投射。没有它们，动物就不能改变前脑机制来抑制内脏脂肪增加。
Hindbrain catecholamine neurons convey gut-derived metabolic signals to an interconnected neuronal network in the hypothalamus and adjacent forebrain. These neurons are critical for short-term glycemic control, glucocorticoid and glucoprivic feeding responses, and glucagon-like peptide 1 (GLP-1) signaling. Here we investigate whether these pathways also contribute to long-term energy homeostasis by controlling obesogenic sensitivity to a high-fat/high-sucrose choice (HFSC) diet. We ablated hindbrain-originating catecholaminergic projections by injecting anti-dopamine-β-hydroxylase-conjugated saporin (DSAP) into the paraventricular nucleus of the hypothalamus (PVH) of male rats fed a chow diet for up to 12 wk or a HFSC diet for 8 wk. We measured the effects of DSAP lesions on food choices; visceral adiposity; plasma glucose, insulin, and leptin; and indicators of long-term ACTH and corticosterone secretion. We also determined lesion effects on the number of carbohydrate or fat calories required to increase visceral fat. Finally, we examined corticotropin-releasing hormone levels in the PVH and arcuate nucleus expression of neuropeptide Y (Npy), agouti-related peptide (Agrp), and proopiomelanocortin (Pomc). DSAP-injected chow-fed rats slowly increase visceral adiposity but quickly develop mild insulin resistance and elevated blood glucose. DSAP-injected HFSC-fed rats, however, dramatically increase food intake, body weight, and visceral adiposity beyond the level in control HFSC-fed rats. These changes are concomitant with1) a reduction in the number of carbohydrate calories required to generate visceral fat,2) abnormalNpy,Agrp, andPomcexpression, and3) aberrant control of insulin secretion and glucocorticoid negative feedback. Long-term metabolic adaptations to high-carbohydrate diets, therefore, require intact forebrain catecholamine projections. Without them, animals cannot alter forebrain mechanisms to restrain increased visceral adiposity.