This longitudinal study addressed the sequential events and metabolic consequences of lipid partitioning following uninephrectomy. Adult male Sprague-Dawley rats were randomized into sham operation (n = 15) or left uninephrectomy (UNX, n = 18). At 1 and 3 months post nephrectomy, three rats from each group were killed for histopathological examination of adipocyte differentiation and lipid accumulation. Renal protein expression of the lipogenic peroxisome proliferator-activated receptor-γ (PPAR-γ), HMG-CoA reductase (HMGCR), and adiponectin receptor was detected by Western blot and immunofluorescence microscopy. Blood lipids, glucose, insulin, and renal functions were longitudinally measured up to 10 months after operation. The UNX rats progressively developed lipodystrophy of subcutaneous and visceral adipose depots with failure of adipocyte differentiation and lipid storage, followed by blood lipid elevation and ectopic lipid deposition with cellular lipid peroxidation, and renal adipogenesis with chronic inflammatory infiltration. Despite having standard diet, normal food consumption and normal body weight, the uninephrectomized rats with defective lipid partitioning manifested a myriad of homeostatic disturbances including insulin resistance, hyperglycemia, adiponectin resistance, and upregulation of PPAR-γ and HMGCR. Abnormal lipid partitioning from adipose depots to circulation and non-adipose tissues and non-adipocytic cells contributes to homeostatic disturbances and lipogenic activation.