Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids.
Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids.
复制标题
作者：
Le Foll C;Dunn-Meynell AA;Miziorko HM;Levin BE
下丘脑腹内侧(VMH)的代谢感觉神经元在周围代谢底物(如葡萄糖和脂肪酸(FA))水平改变时，其活动也会改变。为了评估喂养时摄入高脂饮食(HFD；60%)与血清和VMH FA水平之间的关系，训练大鼠在每天3h内摄入低脂饮食(LFD；13.5%)或HFD，并使用VMH FA微透析进行监测。与LFD大鼠相比，HFD大鼠虽然血清水平较高，但VMH FA水平较低，但在3~6h进食量较少。然而，肾衰大鼠在再喂养的前1h，VMHβ-羟丁酸(β-OHb)水平和VMH-血清β-OHb比值较高，提示VMH星形胶质细胞酮的产生参与了其摄入量的减少。事实上，在分离的VMH神经元中使用钙成像技术表明，酮小体覆盖了正常的FA感觉，主要是通过兴奋被油酸激活或抑制的神经元。重要的是，用3-羟基-3-甲基戊二酰辅酶A合成酶抑制剂双侧抑制VMH酮的产生，逆转了3-6-h HFD引起的摄取抑制，但对LFD喂养的大鼠没有影响。这些数据表明，由于FA诱导星形胶质细胞产生VMH酮体，限制HFD摄入方案可抑制热量摄入。
Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes.
登录
查看更多内容
影响因子：
82.9
作者：
Obici, S;Feng, ZH;Rossetti, L
通讯作者：
Rossetti, L
DOI：
10.1152/ajpregu.00862.2006
发表时间：
2008-02-01
影响因子：
2.8
作者：
Aja, Susan;Landree, Leslie E.;Ronnett, Gabriele V.
通讯作者：
Ronnett, Gabriele V.
影响因子：
5.5
作者：
Murphy, Beth Ann;Fakira, Kurt A.;Routh, Vanessa H.
通讯作者：
Routh, Vanessa H.
影响因子：
4.9
作者：
Duca, F. A.;Swartz, T. D.;Covasa, M.
通讯作者：
Covasa, M.
影响因子：
4.8
作者：
Montgomery, Christa;Pei, Zhengtong;Miziorko, Henry M.
通讯作者：
Miziorko, Henry M.