Here we show that the PPARg2 isoform may be an important factor controlling obesity-induced comorbidities through two mechanisms: (a) by regulating nutritionally induced adipose tissue expandability and (b) when de novo expressed in nonadipose tissues, by allowing the storage of energy in the form of relatively harmless TAG species. The gene discussed is PPARG; the disease is obesity due to melanocortin 4 receptor deficiency.