Abstract：
Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid β-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.
摘要：
富含饱和脂肪的饮食比含有单脂肪或不饱和脂肪的饮食对健康更有害。脂肪酸是能量的重要来源,但它们也将有关营养状态的信息传递给下丘脑代谢回路，当它们过量时可能对这些回路有害。星形胶质细胞是中心脂肪酸β-氧化的主要部位,下丘脑星形胶质细胞参与能量稳态，部分是通过调节到达代谢神经元的激素和营养信号，以及对高脂肪饮食的炎症反应。因此，我们假设下丘脑星形胶质细胞过程特异性脂肪酸如何参与决定差异代谢反应,并且这是性别依赖性的,因为男性和女性对高脂饮食的反应不同.用油酸（OA）或棕榈酸（PA）处理男性和女性原发性下丘脑星形胶质细胞培养物24小时，并进行了非靶向代谢组学研究.获得了明确的PA暴露预测模型，而OA暴露后的代谢组与对照组没有差异。在代谢物中观察到的修饰，以及关键代谢酶的表达水平，表明响应于PA的Krebs和谷氨酸/谷氨酰胺循环的活性降低。此外,雄性和雌性小鼠星形胶质细胞的反应之间存在特定差异，以及下丘脑和大脑皮层星形胶质细胞之间。因此，下丘脑星形胶质细胞对特定脂肪酸的反应可能导致对周围代谢神经元的不同影响，并导致不同的全身代谢结果。
