IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity.

ABSTRACT:

Objective

A causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues.

Methods

17 WT and 13 Irx5 knockout (KO) mice were fed low-fat control (Ctr) or high-fat (HF) diet for 10 weeks. Body weight, energy intake and fat mass were measured. Irx5-dependent gene expression was explored by transcriptome analysis of epididymal white adipose tissue (eWAT), confirmatory obesity-dependent expression in human adipocytes in vivo, and in vitro knock-down, overexpression and transcriptional activation assays.

Results<

SUBMITTER: Bjune JI 

PROVIDER: S-EPMC6451637 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature