Comprehensive metabolic and multiomic phenotyping demonstrated that adipocyte-specific Lpin1–/– mice had a metabolically unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of metabolically associated steatohepatitis that was exacerbated by high-fat diets. The gene discussed is LPIN1; the disease is fatty liver disease.