Adermark Louise, Gutierrez Saray, Lagström Oona, Hammarlund Maria, Licheri Valentina, Johansson Maria E
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden; Deparment of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Psychoneuroendocrinology. 2021 Apr;126:105143. doi: 10.1016/j.psyneuen.2021.105143. Epub 2021 Jan 19.
Overconsumption of food is a major health concern in the western world. Palatable food has been shown to alter the activity of neural circuits, and obesity has been linked to alterations in the connectivity between the hypothalamus and cortical regions involved in decision-making and reward processing, putatively modulating the incentive value of food. Outlining neurophysiological adaptations induced by dietary intake of high fat diets (HFD) is thus valuable to establish how the diet by itself may promote overeating. To this end, C57BL/6 mice were fed HFD rich in either saturated fatty acids (HFD-S) or polyunsaturated fatty acids (HFD-P), or a low-fat control diet (LFD) for four weeks. Food and energy intake were monitored and ex vivo electrophysiology was employed to assess neuroadaptations in lateral hypothalamus (LH) and corticostriatal circuits, previously associated with food intake. In addition, the effects of dietary saturated and polyunsaturated fatty acids on the gene expression of NMDA, AMPA and GABA receptor subunits in the hypothalamus were investigated. Our data shows that mice fed HFD-P had increased daily food and energy intake compared with mice fed HFD-S or LFD. However, this increase in energy intake had no obesogenic effects. Electrophysiological recordings demonstrated that HFD-P had a selective effect on glutamatergic neurotransmission in the LH, which was concomitant with a change in mRNA expression of AMPA receptor subtypes Gria1, Gria3 and Gria4, with no effect on the mRNA expression of NMDA receptor subtypes or GABA receptor subtypes. Furthermore, while synaptic output from corticostriatal subregions was not significantly modulated by diet, synaptic plasticity in the form of long-term depression (LTD) was impaired in the dorsomedial striatum of mice fed HFD-S. In conclusion, this study suggests that the composition of fatty acids in the diet not only affects weight gain, but may also modulate neuronal function and plasticity in brain regions involved in food intake.
食物摄入过量是西方世界主要的健康问题。美味食物已被证明会改变神经回路的活动，肥胖与下丘脑和参与决策及奖励处理的皮质区域之间的连接改变有关，推测这会调节食物的激励价值。因此，概述高脂饮食（HFD）摄入所诱导的神经生理适应性变化，对于确定饮食本身如何促进暴饮暴食具有重要意义。为此，将C57BL/6小鼠分为三组，分别喂食富含饱和脂肪酸的高脂饮食（HFD-S）、富含多不饱和脂肪酸的高脂饮食（HFD-P）或低脂对照饮食（LFD），持续四周。监测食物和能量摄入量，并采用离体电生理学方法评估外侧下丘脑（LH）和皮质纹状体回路中先前与食物摄入相关的神经适应性变化。此外，还研究了饮食中的饱和脂肪酸和多不饱和脂肪酸对下丘脑NMDA、AMPA和GABA受体亚基基因表达的影响。我们的数据表明，与喂食HFD-S或LFD的小鼠相比，喂食HFD-P的小鼠每日食物和能量摄入量增加。然而，这种能量摄入的增加并没有致肥胖作用。电生理记录表明，HFD-P对LH中的谷氨酸能神经传递有选择性影响，这与AMPA受体亚型Gria1、Gria3和Gria4的mRNA表达变化相关，而对NMDA受体亚型或GABA受体亚型的mRNA表达没有影响。此外，虽然饮食对皮质纹状体亚区域的突触输出没有显著调节作用，但喂食HFD-S的小鼠背内侧纹状体中以长时程抑制（LTD）形式存在的突触可塑性受损。总之，本研究表明饮食中脂肪酸的组成不仅影响体重增加，还可能调节参与食物摄入的脑区中的神经元功能和可塑性。
