Farnesoid X Receptor alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements. Mus musculus

The bile acid-activated nuclear receptor Farnesoid X receptor (FXR, NR1H4) has been implicated in the control of lipid and energy metabolism, but its role in fat tissue, where it is moderately expressed, is not understood. In view of the recent development of FXR-targeting therapeutics for treatment of human metabolic diseases, understanding the tissue-specific actions of FXR is essential. We show that transgenic mice expressing human FXR specifically in adipose tissue (aP2-hFXR) have markedly enlarged adipocytes and show extensive extracellular matrix remodelling. Ageing and exposure to obesogenic conditions revealed a strongly limited capacity for adipose expansion and development of fibrosis in adipose tissues of aP2-hFXR transgenic mice. This was associated with impaired lipid storage capacity, leading to elevated plasma free fatty acids, ectopic fat deposition in liver and muscle as well as whole-body insulin resistance. These studies establish that adipose FXR is a determinant of adipose tissue architecture and contributes to whole-body lipid homeostasis. Overall design: Total RNA optained from 10 BAT and 8 WAT samples, where compaired in 2 by 2 different groups, consisting of biological replicates n=4,5