CRCHUM and Montreal Diabetes Research Centre; Department of Nutrition, Faculty of Medicine, Université de Montreal, Montreal, Quebec, Canada.
Int J Obes (Lond). 2013 Sep;37(9):1183-91. doi: 10.1038/ijo.2012.197. Epub 2012 Dec 11.
To identify the emotional and motivational processes that reinstate palatable food intake following removal of high-fat diet (HFD) and associated neuroadaptations tied to neurochemical and behavioural changes underlying dopaminergic function.
Adult male C57Bl6 mice were placed on a HFD (58% kcal fat) or ingredient-matched, low-fat diet (LFD; 11% kcal fat) for 6 weeks. At the end of diet-regimen mice were either maintained on their respective diets, or HFD and LFD were replaced with normal chow (withdrawal). Effort-based operant responding for sucrose and high-fat food rewards was measured along with basal and stress-induced corticosterone levels and anxiety (elevated-plus maze). Protein levels for tyrosine hydroxylase (TH), corticosterone releasing factor type 1 receptor (CRF-R1), brain-derived neurotrophic factor (BDNF), phospho-CREB (pCREB) and ΔFosB (truncated splice variant of FosB) were assessed in the amygdala, nucleus accumbens (NAc) and ventral tegmental area (VTA) via western immunoblotting.
Six weeks of HFD resulting in significant weight gain elicited sucrose anhedonia, anxiety-like behaviour and hypothalamic-pituitary-adrenocortical axis (HPA) hypersensitivity to stress. Withdrawal from HFD but not LFD-potentiated anxiety and basal corticosterone levels and enhanced motivation for sucrose and high-fat food rewards. Chronic high-fat feeding reduced CRF-R1 and increased BDNF and pCREB protein levels in the amygdala and reduced TH and increased ΔFosB protein in NAc and VTA. Heightened palatable food reward in mice withdrawn from HFD coincided with increased BDNF protein levels in NAc and decreased TH and pCREB expression in the amygdala.
Anhedonia, anxiety and sensitivity to stressors develops during the course of HFD and may have a key role in a vicious cycle that perpetuates high-fat feeding and the development of obesity. Removal of HFD enhances stress responses and heightens vulnerability for palatable foods by increasing food-motivated behaviour. Lasting changes in dopamine and plasticity-related signals in reward circuitry may promote negative emotional states, overeating and palatable food relapse.
确定在去除高脂肪饮食 (HFD) 后恢复美味食物摄入的情绪和动机过程，以及与多巴胺能功能相关的神经化学和行为变化的基础上，与神经适应相关的。
成年雄性 C57Bl6 小鼠接受高脂肪饮食 (HFD; 58%卡路里脂肪) 或成分匹配的低脂肪饮食 (LFD; 11%卡路里脂肪) 6 周。在饮食方案结束时，将小鼠维持在各自的饮食上，或用普通食物替代 HFD 和 LFD(戒断)。通过基础和应激诱导的皮质酮水平和焦虑(高架十字迷宫)来测量蔗糖和高脂肪食物奖赏的基于努力的操作性反应。通过 Western 免疫印迹法评估杏仁核、伏隔核 (NAc) 和腹侧被盖区 (VTA) 中的酪氨酸羟化酶 (TH)、皮质酮释放因子 1 型受体 (CRF-R1)、脑源性神经营养因子 (BDNF)、磷酸化 CREB(pCREB) 和 ΔFosB(FosB 的截断剪接变体)的蛋白水平。
6 周的 HFD 导致体重显著增加，引起蔗糖快感缺失、焦虑样行为和下丘脑-垂体-肾上腺皮质轴 (HPA) 对压力的敏感性增加。从 HFD 中退出而不是从 LFD 中退出，增强了焦虑和基础皮质酮水平，并增强了蔗糖和高脂肪食物奖赏的动机。慢性高脂肪喂养降低了杏仁核中的 CRF-R1 并增加了 BDNF 和 pCREB 蛋白水平，降低了 NAc 和 VTA 中的 TH 和增加了 ΔFosB 蛋白。从 HFD 中退出的小鼠对美味食物奖赏的反应增强，与 NAc 中的 BDNF 蛋白水平升高以及杏仁核中的 TH 和 pCREB 表达降低有关。
快感缺失、焦虑和对压力源的敏感性在 HFD 过程中发展，可能在促进高脂肪喂养和肥胖发展的恶性循环中发挥关键作用。去除 HFD 通过增加食物驱动的行为，增强了应激反应，并增加了对美味食物的脆弱性。奖励回路中多巴胺和可塑性相关信号的持久变化可能会促进负面情绪状态、暴饮暴食和美味食物的复发。
