FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements.

ABSTRACT: The bile acid-activated nuclear 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. Transgenic mice expressing human FXR in adipose tissue (aP2-hFXR mice) at three to five times higher levels than endogenous Fxr, i.e., much lower than its expression in liver and intestine, have markedly enlarged adipocytes and show extensive extracellular matrix remodeling. Ageing and exposure to obesogenic conditions revealed a strongly limited capacity for adipose expansion and development of fibrosi

SUBMITTER: van Zutphen T 

PROVIDER: S-EPMC6718433 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature