To delineate whether Atglistatin exerts its anti-obesity effects by an Atgl-dependent or -independent ‘off-target' effect, we fed ‘cardiac-rescued' Atgl-deficient (AKO/cTg) and control animals a HFD±Atglistatin. The gene discussed is PNPLA2; the disease is obesity due to melanocortin 4 receptor deficiency.