Here, we show that mice lacking HOIP, the Lin-E3 ligase catalytic subunit of LUBAC, in adipocytes (HoipA-KO) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). The gene discussed is RNF31; the disease is metabolic dysfunction-associated steatotic liver disease.