Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Department of Experimental Medical Science, Faculty of Medicine, Lund University, Lund, Sweden.
Int J Obes (Lond). 2019 Jun;43(6):1295-1304. doi: 10.1038/s41366-018-0224-9. Epub 2018 Oct 9.
BACKGROUND/OBJECTIVES: High-fat diet consumption is known to trigger an inflammatory response in the hypothalamus, which has been characterized by an initial expression of pro-inflammatory genes followed by hypothalamic astrocytosis, microgliosis, and the appearance of neuronal injury markers. The specific effects of high-fat diet on hypothalamic energy metabolism and neurotransmission are however not yet known and have not been investigated before.
SUBJECTS/METHODS: We used H and C magnetic resonance spectroscopy (MRS) and immunofluorescence techniques to evaluate in vivo the consequences of high-saturated fat diet administration to mice, and explored the effects on hypothalamic metabolism in three mouse cohorts at different time points for up to 4 months.
We found that high-fat diet increases significantly the hypothalamic levels of glucose (P < 0.001), osmolytes (P < 0.001), and neurotransmitters (P < 0.05) from 2 months of diet, and alters the rates of metabolic (P < 0.05) and neurotransmission fluxes (P < 0.001), and the contribution of non-glycolytic substrates to hypothalamic metabolism (P < 0.05) after 10 weeks of high-fat feeding.
CONCLUSIONS/INTERPRETATION: We report changes that reveal a high-fat diet-induced alteration of hypothalamic metabolism and neurotransmission that is quantifiable by H and C MRS in vivo, and present the first evidence of the extension of the inflammation pathology to a localized metabolic imbalance.
背景/目的：高脂饮食摄入已知会引发下丘脑的炎症反应，其特征为最初表达促炎基因，随后出现下丘脑星形胶质细胞增生、小胶质细胞增生和神经元损伤标志物出现。然而，高脂饮食对下丘脑能量代谢和神经传递的确切影响尚不清楚，以前也没有进行过研究。
受试者/方法：我们使用 H 和 C 磁共振波谱（MRS）和免疫荧光技术来评估高脂肪饮食对小鼠的体内后果，并在三个不同时间点的三个小鼠队列中探索其对下丘脑代谢的影响，最长可达 4 个月。
我们发现高脂肪饮食从 2 个月开始显著增加下丘脑的葡萄糖水平（P<0.001）、渗透压物质（P<0.001）和神经递质水平（P<0.05），并改变代谢率（P<0.05）和神经传递通量（P<0.001），以及非糖酵解底物对下丘脑代谢的贡献（P<0.05）在 10 周高脂肪喂养后。
结论/解释：我们报告的变化表明，高脂肪饮食引起的下丘脑代谢和神经传递改变可通过体内 H 和 C MRS 进行定量检测，并首次证明炎症病理学扩展到局部代谢失衡。
