Obesity and Food Choice Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK.
AstraZeneca, Mereside, Macclesfield, UK.
J Neuroendocrinol. 2017 Aug;29(8). doi: 10.1111/jne.12498.
Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high-fat (HF) diet for 2 hours a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2-hour scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs 24 hours ad libitum feeding on the same HF diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine- and amphetamine-regulated transcript, pro-opiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), as well as enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain, were measured by in situ hybridisation. Mice fed ad libitum on a HF diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, although they did not appear to be related to feeding behaviour in the schedule-fed groups (ie, the large, binge-type meals) and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, although it still leaves open the fundamental question about the underlying mechanisms of meal feeding.
在不限制热量的情况下，观察 C57BL/6 小鼠定时进食时下丘脑稳态和前脑奖励相关基因。自由进食但每天允许摄入高脂肪（HF）饮食 2 小时的小鼠迅速适应了它们的进食行为，并且在这段 2 小时的定时进食中消耗了大约 80%的每日热量摄入。在相同的 HF 饮食上，通过原位杂交法检测在定时进食的第一或第二小时与 24 小时自由进食相比，下丘脑弓状核（ARC）中的神经肽 Y、肥胖相关肽、可卡因和安非他命调节转录物、前阿黑皮素原、长形式瘦素受体和细胞因子信号抑制物-3 的基因表达水平，以及前脑伏隔核（NAcc）中的脑啡肽、强啡肽、多巴胺-2-受体和多巴胺-3-受体。自由进食 HF 饮食的小鼠总热量摄入、体重增加、脂肪量和血清瘦素最高，而定时进食的小鼠则表现出轻度肥胖表型，总热量摄入、体重增加、脂肪量和血清瘦素处于中间水平。进食方式对 ARC 基因表达的影响通过与体重增加、脂肪量和血液瘦素的显著正相关或负相关而被强调，尽管它们似乎与定时进食组的进食行为无关（即，大量、暴食型的进食），并且没有发现任何潜在的候选基因来调节这些进食。大餐/暴食型进食的机制可能受非稳态愉悦过程调节。然而，对 NAcc 中阿片类和多巴胺受体基因表达的评估并未显示这些基因参与调节大餐。这补充了我们之前对定时进食的小鼠和大鼠 ARC 和 NAcc 基因的描述，尽管它仍然留下了关于进食机制的基本问题。
