Obese individuals are at high risk of developing kidney disease, which can lead to renal failure requiring dialysis or transplant. Few models of obesity-associated kidney disease exist, so investigating the association has been a challenge. Martínez-García et al. now report a model that enables the study of kidney disease in the context of obesity. They crossed ob/ob mice (which store large amounts of fat) with mice lacking PPARγ (which are impaired in generating fat tissue) to generate ‘POKO mice’, which have high circulating levels of glucose and fat. At just 4 weeks old, POKO mice show kidney dysfunction associated with inflammation, fibrosis and lipid accumulation – all signs of advanced kidney disease. Kidney pathology advances to severe by 12 weeks. These data introduce the POKO mouse as a new model of obesity-associated kidney disease, and indicate that glucolipotoxicity can accelerate the condition. Page 636

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