Peripheral Serotonin Enhances Lipid Metabolism by Accelerating Bile Acid Turnover

Abstract

Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the brain and one in the periphery. The latter is known to be unable to cross the blood-brain barrier. These two serotonin systems have apparently independent functions, although the functions of peripheral serotonin have yet to be fully elucidated. In this study, we have investigated the physiological effect of peripheral serotonin on the concentrations of metabolites in the circulation and in the liver. After fasting, mice were ip injected with 1 mg serotonin. The plasma glucose concentration was significantly elevated between 60 and 270 min after the injection. In contrast, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations were decreased. The hepatic glycogen synthesis and concentrations were significantly higher at 240 min. At the same time, the hepatic triglyceride content was significantly lower than the basal levels noted before the serotonin injection, whereas the hepatic cholesterol content was significantly higher by 60 min after the injection. Furthermore, serotonin stimulated the contraction of the gallbladder and the excretion of bile. After the serotonin injection, there was a significant induction of apical sodium-dependent bile acid transporter expression, resulting in a decrease in the concentration of bile acids in the feces. Additionally, data are presented to show that the functions of serotonin are mediated through diverse serotonin receptor subtypes. These data indicate that peripheral serotonin accelerates the metabolism of lipid by increasing the concentration of bile acids in circulation.

Energy Homeostasis by the Peripheral Serotonergic System

“…Nevertheless, not all studies agree. Injection of serotonin does not impact on the uptake of 2-deoxy-glucose in the liver of fasted mice [10]. Additionally, in an experiment using conscious dogs, portal vein injection of serotonin induced hepatic glucose uptake during a hyperinsulinemic-euglycemic clamp [21].…”

“…Additionally, it has been reported that serotonin injection elevates plasma insulin levels [10,11]. Therefore, serotonin might regulate insulin secretion from β cells by both local and systemic actions.…”

“…By stimulating the contraction of the smooth muscle in the gallbladder, serotonin induces the excretion of bile acids in a direct manner from the gallbladder into the duodenum [27,28]. In addition to the excretion of bile acids from the gallbladder, serotonin is reported to enhance reabsorption of bile acids from the ileum and raise the level of plasma bile acids (Figure 2) [10]. Serotonin injection has been shown to cause an elevation of the expression of the apical sodium-dependent bile acid transporter (ASBT), which actively causes the reabsorption of bile acids from the lumen of the intestine into the body and decreases the content of bile acids in the feces.…”

“…It has been suggested that serotonin may affect the concentrations of lipid in the liver and blood [10]. In practical terms, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations are reduced following serotonin injection.…”

Role of Serotonin in the Regulation of Respiration and Bile Secretory Function of the Liver

“…Однак питання впливу цього бі-огенного аміну на секрецію жовчі, як одного із показників, що відображає функціональний стан печінки, є недостатньо вивченим. До того ж, аналіз концентрацій таких специфіч-них компонентів жовчі, як жовчні кислоти здійснювався лише у плазмі крові [11,12]. Секреція -жовчі це складний багатоетапний процес, що відбувається за участі переважно киснезалежних процесів [13], таких, зокре-ма, як синтез жовчних кислот [14].…”