Here, we report that a novel TZD analog MSDC-0602K (“TZD of second generation or PPARγ-sparing TZD”), purposely designed to have a weak binding affinity to PPARγ, manifested less detrimental effects on metabolic and molecular properties of bone and mBM-MSCs in HFD-induced obesity in male mice compared with the classical TZD pioglitazone. This evidence concerns the gene PPARG and Obesity.