Epididymal fat Transcriptome in CF mice. Mus musculus

Cystic fibrosis (CF) is a lethal genetic disorder that affects most organ systems of the body, including the endocrine and exocrine systems. Health and survival associate with body mass and as a consequence, CF clinical care includes high-fat, high-calorie diets to maintain, and even 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 use mouse models of CF, which also display small adipose stores, to begin examining body fat as a prelude into mechanistic studies of low bodily growth in CF, so that optimal therapeutic strategies can 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 the volume of intraperitoneal and subcutaneous adipocytes. We found smaller, but not fewer, adipocytes in CF compared to WT animals. Specifically, intraperitoneal CF adipocytes were half the volume of WT cells, whereas subcutaneous cells were less affected by 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, Pck, Jun), consistent with low triglyceride storage. The data indicate that CF adipocytes contain less triglycerides than WT cells and a role for CFTR in these cells is proposed.