Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1

•GPS2 depletion in human adipose-derived mesenchymal stem cells increases expression of adipogenic genes, including BMP4.•Loss of GPS2 leads to coordinated changes of epigenome and transcriptome during human adipocyte differentiation.•Loss of GPS2 upregulates ABCG1 and LPL and induces lipidome remodeling including sphingomyelin depletion.•The GPS2-ABCG1 pathway contributes to adipocyte hypertrophy.•GPS2 and ABCG1 levels in omental adipose tissue inversely correlate with type 2 diabetes in obese humans.