SPP1 and obesity due to melanocortin 4 receptor deficiency: Osteopontin induces brown adipogenesis in cultured preadipocytes through the activation of the PI3K/Akt pathway in a CD44-dependent manner and the downregulation of OPN in WAT of mice exacerbates obesity and inhibits WAT browning via the inhibition of PPARγ-mediated activation of PI3K/Akt signaling [372,373,374].