Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Centre for Discovery Brain Sciences, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Elife. 2024 Jul 8;12:RP93052. doi: 10.7554/eLife.93052.
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated waith AMP-activated protein kinase, peroxisome proliferator-activated receptor alpha, mammalian target of rapamycin, and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to food restriction.
哺乳动物已经进化出性别特异性的适应机制，以在食物匮乏时减少能量消耗。这些适应机制在外周组织中得到了很好的描述，尽管人们对能量密集型大脑如何适应食物限制以及这些适应机制在性别之间的差异知之甚少。在这里，我们研究了食物限制如何影响成年雄性和雌性小鼠大脑初级视觉皮层（V1）的能量消耗和功能。V1 中的分子分析和 RNA 测序显示，在雄性小鼠中，但在雌性小鼠中并非如此，食物限制显著调节了经典的、与能量调节相关的途径，包括与 AMP 激活蛋白激酶、过氧化物酶体增殖物激活受体 α、雷帕霉素哺乳动物靶标和氧化磷酸化相关的途径。此外，我们发现与雄性小鼠相反，食物限制并没有显著影响雌性小鼠 V1 的 ATP 使用或视觉编码精度（通过取向选择性评估）。众所周知，血清瘦素的降低是触发 V1 中节能变化所必需的。与此一致，我们发现食物限制的雄性小鼠血清瘦素显著降低，但食物限制的雌性小鼠没有明显变化。总之，我们的研究结果表明，与雄性小鼠相比，雌性小鼠的皮层功能和能量消耗对食物限制的适应能力更强。因此，新皮层有助于对食物限制做出性别特异性的节能适应。
