Inter-organ communications mediate crosstalk between glucose and energy metabolism

Obesity-associated diabetes, a major risk factor for numerous disorders including chronic renal, cardiovascular, and cerebrovascular diseases, is a rapidly increasing public health challenge worldwide. Despite several remarkable advances in obesity research over the past decade, the mechanisms underlying obesity are still not fully understood. In recent years it has been revealed that several metabolic interactions between organs and tissues, which are mediated by neuronal networks governed by the brain, function as a negative-feedback mechanism to maintain body weight homeostasis, even when energy intake is excessive. On the other hand, we recently discovered a new inter-organ neural network, from the liver, possibly representing a positive-feedback mechanism. In states of energy intake beyond physiological requirements, glucose metabolism changes in the liver with increased hepatic glucokinase expression and the induction of neuronal signal transmissions via the afferent vagal nerve. These signals, received by the medulla, result in inactivation of sympathetic innervation of brown adipose tissue (BAT). This leads to suppression of thermogenesis in BAT and thereby favors obesity development. This review focuses on the neuronal network mediating the inter-organ communication necessary for glucose and energy metabolism.