Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet.
Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet.
复制标题
DOI：
10.1016/j.physbeh.2017.03.040
复制
发表时间：
2017-07-01
影响因子：
2.9
通讯作者：
Kotz CM
中科院分区：
文献类型：
--
作者：
Bunney PE;Zink AN;Holm AA;Billington CJ;Kotz CM
超重和肥胖是由于热量摄入和能量消耗之间的不平衡造成的，包括自发身体活动（SPA）的消耗。SPA的变化和由此引起的非运动活动产热（NEAT）的变化可能与饮食相互作用，影响肥胖风险。然而，之前关于饮食、身体活动和能量消耗之间关系的研究结果好坏参半。神经肽orexin是SPA的驱动因子，orexin神经元的活性可以通过设计药物特异性激活的设计受体（DREADDs）来控制。我们假设HFD会降低SPA和NEAT，而redd介导的食欲素神经元信号的激活会消除这种减少并产生NEAT的增加。为了验证这些观点，我们对行为进行了表征，以确定获得高脂肪饮食（HFD）对参与食物摄入和活动的比例和概率的影响程度。然后，我们在获得HFD和针对食欲素神经元的DREADD干预后测量了NEAT。研究人员将一种兴奋性的DREADD病毒注射到食欲素神经元集中的尾侧下丘脑，这是两组有食欲素的雄性小鼠。然后将小鼠安置在连续代谢表型笼（貂Promethion）中。每秒钟自动测量食物摄取量、间接量热和SPA。在队列1 （n=8）中，给动物喂食食物，然后切换到HFD。对于队列2 （n=4/组），一半的动物给予HFD，另一部分给予chow。然后，在高热量饮食的动物中，进食素神经元在注射氯氮平n-氧化物（CNO）后被激活。饲喂高脂饲料的小鼠进食时间明显少于饲喂饲料的小鼠（p<0.01），而不活动时间明显多于饲喂饲料的小鼠（p<0.01）。餐后，喂食高热量食物的小鼠比喂食食物的小鼠更有可能处于静止状态（p<0.05）。高热量饮食动物的NEAT水平下降，而在用DREADDs激活食欲素神经元后，对照组动物的NEAT水平上升。食物摄取量（千卡）在喂食鼠和食用HFD的小鼠之间没有显著差异，但喂食鼠每单位SPA消耗的能量高于喂食HFD的小鼠。这些结果表明，食用高热量食物会减少SPA和NEAT，并增加餐后不活动。综上所述，这些数据表明，能量消耗效率的变化是基于饮食的，例如，与标准饮食相比，高热量饮食期间的SPA消耗的卡路里更少。
Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.
登录
查看更多内容
影响因子：
--
作者：
Kotz, CM;Teske, JA;Wang, CF
通讯作者：
Wang, CF
影响因子：
4.2
作者：
Eumann Mesas, Arthur;Guallar-Castillon, Pilar;Rodriguez-Artalejo, Fernando
通讯作者：
Rodriguez-Artalejo, Fernando
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.
DOI：
10.1073/pnas.0811126106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Matsuki, Taizo;Nomiyama, Mika;Sakurai, Takeshi
通讯作者：
Sakurai, Takeshi
影响因子：
3.6
作者：
Choi, Myung-Sook;Kim, Young-Je;Jung, Un Ju
通讯作者：
Jung, Un Ju