Small adipose stores in cystic fibrosis mice are characterized by reduced cell volume, not cell number

Abstract

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.