Schematic representation of the physiological functions affected by osteocalcin, lipocalin 2 and FGF23, the three known osteoblast-derived hormones. Osteocalcin stimulates insulin secretion in the pancreas, insulin sensitivity in adipose tissue, nutrients uptake and catabolism inmuscle and testosterone production in the testis. In β-cells, the Leydig cells of the testis and in myofibers, osteocalcin signals through Gprc6a. In addition, osteocalcin promotes monoamine neurotransmitter synthesis and cognitive functions in the brain. FGF23 acts in the kidney to favor phosphate elimination. FGFR1 and Klotho mediate FGF23 signal in the tubular cells of the kidney. Lipocalin 2 binds to the melanocortin 4 receptor in neurons of the hypothalamus to inhibit food intake.