This includes targeted studies showing reduced markers of mitochondrial content and function in SAT of obese (db/db) mice [33] as well as unbiased, omics-based studies showing impaired mitochondrial biogenesis in individuals with acquired obesity compared with their lean co-twins [12,34] and reduced expression of genes involved in OXPHOS and the TCA cycle in obese, insulin-resistant individuals [11,20,35]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.