The consequences of excessive fructose intake extend beyond those of metabolic disorder to changes in emotional regulation and cognitive function. Long-term consumption of fructose, particularly common when begun in adolescence, is more likely to lead to deleterious consequences than acute consumption. These long-term consequences manifest differently in males and females, suggesting a sex-divergent mechanism by which fructose can impair physiology and neural function. The purpose of the current project was to investigate a possible sex-specific mechanism by which elevated fructose consumption drives behavioral deficits and accompanying metabolic symptoms - specifically, synaptic mitochondrial function. Male and female rats were fed a high fructose diet beginning at weaning and maintained into adulthood. Measures of physiological health across the diet consumption period indicated that females were more likely to gain weight than males while both displayed increased circulating blood glucose. As adults, females fed the high fructose diet displayed increased floating behavior in the forced swim task while males exhibited increased exploratory behavior in the open field. Synaptic respiration was altered by diet in both females and males but the effect was sex-divergent - fructose-fed females had increased synaptic respiration while males showed a decrease. When exposed to an acute energetic challenge, the pattern was reversed. Taken together, these data indicate that diet-induced alterations to neural function and physiology are sex-specific and highlight the need to consider sex as a biological variable when treating metabolic disease. Furthermore, these data suggest that synaptic mitochondrial function may contribute directly to the behavioral consequences of elevated fructose consumption.

中文翻译：

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高果糖饮食诱导大鼠突触呼吸和情感样行为的性别特异性改变。

果糖摄入过多的后果不仅限于代谢紊乱，还包括情绪调节和认知功能的变化。长期食用果糖，尤其是在青春期开始时尤其常见，与急性食用相比，更可能导致有害后果。这些长期后果在男性和女性中的表现不同，这表明果糖可以损害生理和神经功能的性别差异机制。当前项目的目的是研究一种可能的性别特异性机制，通过该机制，果糖消耗升高会导致行为缺陷和伴随的代谢症状——特别是突触线粒体功能。雄性和雌性大鼠从断奶开始喂食高果糖饮食并维持到成年。整个饮食消费期间的生理健康指标表明，女性比男性更容易增加体重，而两者都表现出循环血糖升高。作为成年人，喂食高果糖饮食的雌性在强迫游泳任务中表现出增加的漂浮行为，而雄性在开阔场地中表现出增加的探索行为。女性和男性的饮食都会改变突触呼吸，但这种影响是性别差异的——喂食果糖的女性增加了突触呼吸，而男性则减少了。当暴露于剧烈的能量挑战时，这种模式就发生了逆转。总之，这些数据表明饮食引起的神经功能和生理学改变具有性别特异性，并强调在治疗代谢疾病时需要将性别视为生物学变量。此外，