Department of Pediatrics, Case Western Reserve University , Cleveland, Ohio.
Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, Ohio.
Am J Physiol Gastrointest Liver Physiol. 2018 Dec 1;315(6):G943-G953. doi: 10.1152/ajpgi.00096.2017. Epub 2018 Sep 6.
Cystic fibrosis (CF) is a lethal genetic disorder that affects many organ systems of the body, including various endocrine and exocrine tissues. Health and survival positively associate with body mass, and as a consequence, CF clinical care includes high-fat, high-calorie diets to maintain and increase adipose tissue stores. Such strategies have been implemented without a clear understanding of the cause and effect relationship between body mass and patients' health. Here, we used CF mouse models, which display small adipose stores, to begin examining body fat as a prelude into mechanistic studies of low body growth in CF, so that optimal therapeutic strategies could be developed. We reasoned that low adiposity must result from reduced number and/or volume of adipocytes. To determine relative contribution of either mechanism, we quantified volume of intraperitoneal and subcutaneous adipocytes. We found smaller, but not fewer, adipocytes in CF compared with wild-type (WT) animals. Specifically, intraperitoneal CF adipocytes were one-half the volume of WT cells, whereas subcutaneous cells were less affected by the Cftr genotype. No differences were found in cell types between CF and WT adipose tissues. Adipose tissue CFTR mRNA was detected, and we found greater CFTR expression in intraperitoneal depots as compared with subcutaneous samples. RNA sequencing revealed that CF adipose tissue exhibited lower expression of several key genes of adipocyte function ( Lep, Pck1, Fas, Jun), consistent with low triglyceride storage. The data indicate that CF adipocytes contain fewer triglycerides than WT cells, and a role for CFTR in these cells is proposed. NEW & NOTEWORTHY Adipocytes in cystic fibrosis mice exhibit smaller size due to low triglyceride storage. Adipocyte cell number per fat pad is similar, implying triglyceride storage problem. The absence of CFTR function in adipose tissue has been proposed as a direct link to low triglyceride storage in cystic fibrosis.
囊性纤维化（CF）是一种致命的遗传疾病，影响身体的许多器官系统，包括各种内分泌和外分泌组织。健康和生存与体重呈正相关，因此，CF 临床护理包括高脂肪、高热量饮食，以维持和增加脂肪组织储存。这些策略的实施并没有清楚地了解体重与患者健康之间的因果关系。在这里，我们使用 CF 小鼠模型，这些模型显示脂肪组织储存量小，开始检查体脂肪，作为 CF 中低体生长的机制研究的前奏，以便开发最佳的治疗策略。我们推断，低脂肪含量必然是由于脂肪细胞数量和/或体积减少所致。为了确定这两种机制的相对贡献，我们对腹腔内和皮下脂肪细胞的体积进行了量化。我们发现 CF 与 WT 相比，脂肪细胞体积较小，但数量没有减少。具体来说，CF 动物的腹腔内脂肪细胞体积是 WT 细胞的一半，而皮下细胞受 Cftr 基因型的影响较小。CF 和 WT 脂肪组织之间的细胞类型没有差异。检测到脂肪组织 CFTRmRNA，并发现与皮下样本相比，腹腔内脂肪组织中 CFTR 的表达更高。RNA 测序表明，CF 脂肪组织中几种关键脂肪细胞功能基因（Lep、Pck1、Fas、Jun）的表达较低，与甘油三酯储存量低一致。数据表明，CF 脂肪细胞中甘油三酯的含量低于 WT 细胞，提出 CFTR 在这些细胞中的作用。新观点和值得注意的观点 CF 小鼠的脂肪细胞由于甘油三酯储存量低而体积较小。每个脂肪垫的脂肪细胞数量相似，这意味着甘油三酯储存存在问题。脂肪组织中 CFTR 功能的缺失被认为是 CF 中甘油三酯储存量低的直接原因。
