Hepatic Rspo3 induction increased β2-adrenergic receptor (β2AR) and resultant PGC1α expressions in skeletal muscle (Fig 4K) [30], thereby suggesting the restoration of adrenergic signaling, and skeletal muscle quality [31], which had been impaired in the setting of obesity. Here, PPARGC1A is linked to obesity due to melanocortin 4 receptor deficiency.