Interactions among bone, liver, and adipose tissue predisposing to diabesity and fatty liver

Growing epidemiological evidence connects obesity and its complications, including metabolic syndrome, diabetes, and nonalcoholic fatty liver disease (NAFLD) to reduced bone health and osteoporosis. Parallel to human studies, experimental data disclosed a complex network of interaction among adipose tissue, the liver, and the bone, which reciprocally modulate the function of each other. The main mediators of such crosstalk include hormonal/cytokine signals from the bone (osteopontin, osteocalcin, and osteoprotegerin), the liver (fetuin-A), and adipose tissue [leptin, tumor necrosis factor-α (TNF-α), and adiponectin]. Dysregulation of this network promotes the development of diabesity, NAFLD, and osteoporosis. We will review recent advances in understanding the mechanisms of bone-liver-adipose tissue interaction predisposing to obesity, diabetes, NAFLD, and osteoporosis and their potential clinical implications.