Low-dose bortezomib treatment reduced TG accumulation on the chow diet group and prevented HFD-induced obesity and fatty liver development in mice by enhancing CerS2 expression, which plays a key role in regulating ER stress and its downstream targets, SREBP-1 cleavage, and lipogenesis. The gene discussed is SREBF1; the disease is obesity due to melanocortin 4 receptor deficiency.