Roles of the interorgan neuronal network in the development of metabolic syndrome

Abstract

Metabolic processes in different tissues and remote organs are under coordinated systemic regulation, allowing adaptation to a variety of external circumstances. Neuronal signals as well as humoral factors, such as nutrients, growth factors, and hormones, have attracted increasing attention for their roles in this interorgan metabolic network, responsible for the maintenance of metabolic homeostasis at the whole-body level. These interorgan communications within an organism are considered to be diverse and, in fact, we identified previously unknown neuronal relay systems originating in the liver which modulate energy, glucose, and lipid metabolism. Furthermore, when nutrient overload is prolonged, these neuronal mechanisms, which function as an endogenous defense system against obesity development, contribute to the pathophysiological states of metabolic syndrome characterized by obesity-associated features. Therefore, these interorgan neuronal systems are considered to be possible molecular targets for treating metabolic syndrome. We herein review the precise mechanisms underlying the functions of the mammalian interorgan neuronal network, especially the pathways from the liver to several other organs, focusing on their significance and roles in the development of metabolic syndrome.

Keywords: Amino acids; Hypertension; Hypertriglyceridemia; Interorgan neuronal network; Metabolic syndrome; PPARγ; mTOR.

Fig. 1

Physiology of the interorgan neuronal network. The interorgan neuronal network traveling from the liver to adipose tissues regulates systemic glucose and energy metabolism. This pathway functions as an endogenous defense mechanism against obesity development under conditions of sustained nutirent overload

Fig. 2

Scheme of the pathophysiology of metabolic syndrome, i.e., obesity-related hypertension. Under the conditions of sustained energy overload often present during obesity development, the interorgan neuronal network, ironically, persistently activates the sympathetic nervous system, leading to pathological states such as obesity-related hypertension

Fig. 3

The pathophysiology of obesity-related hypertriglyceridemia, a hallmark of metabolic syndrome. The interorgan (liver to adipose) neuronal network is responsible for a novel form of internutrient (AA to lipid) coordination. Sustained overnutrition during obesity development excessively activates this regulatory system, leading to pathological states such as obesity-related hypertriglyceridemia