Sheng Ming, Hosseinzadeh Ava, Muralidharan Somsundar Veppil, Gaur Rahul, Selstam Eva, Tuck Simon
Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden.
Department of Plant Physiology, Umeå University, SE-901 87 Umeå, Sweden.
PLoS One. 2015 Apr 7;10(4):e0124515. doi: 10.1371/journal.pone.0124515. eCollection 2015.
The molecular mechanisms by which dietary fatty acids are absorbed by the intestine, and the way in which the process is regulated are poorly understood. In a genetic screen for mutations affecting fat accumulation in the intestine of Caenorhabditis elegans, nematode worms, we have isolated mutations in the aex-5 gene, which encodes a Kex2/subtilisin-family, Ca2+-sensitive proprotein convertase known to be required for maturation of certain neuropeptides, and for a discrete step in an ultradian rhythmic phenomenon called the defecation motor program. We demonstrate that aex-5 mutants have markedly lower steady-state levels of fat in the intestine, and that this defect is associated with a significant reduction in the rate at which labeled fatty acid derivatives are taken up from the intestinal lumen. Other mutations affecting the defecation motor program also affect steady-state levels of triglycerides, suggesting that the program is required per se for the proper accumulation of neutral lipids. Our results suggest that an important function of the defecation motor program in C. elegans is to promote the uptake of an important class of dietary nutrients. They also imply that modulation of the program might be one way in which worms adjust nutrient uptake in response to altered metabolic status.
饮食中的脂肪酸被肠道吸收的分子机制以及该过程的调节方式目前仍知之甚少。在一项针对影响秀丽隐杆线虫（一种线虫）肠道脂肪积累的突变进行的基因筛选中，我们分离出了aex - 5基因的突变。该基因编码一种Kex2/枯草杆菌蛋白酶家族的、对钙离子敏感的前体蛋白转化酶，已知该酶对于某些神经肽的成熟以及一种名为排便运动程序的超日节律现象中的一个离散步骤是必需的。我们证明，aex - 5突变体肠道中的脂肪稳态水平显著降低，并且这种缺陷与标记脂肪酸衍生物从肠腔吸收的速率显著降低有关。其他影响排便运动程序的突变也会影响甘油三酯的稳态水平，这表明该程序本身对于中性脂质的正常积累是必需的。我们的结果表明，秀丽隐杆线虫中排便运动程序的一个重要功能是促进一类重要膳食营养素的吸收。它们还暗示，对该程序的调节可能是线虫根据代谢状态改变来调整营养吸收的一种方式。
