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Fasting induced changes in hepatic thyroid hormone metabolism in male rats are independent of autonomic nervous input to the liver

Onderzoeksgroep Kalsbeek
Publicatiejaar 2014
Gepubliceerd in Endocrinology
Auteur(s) A. Kalsbeek ,

During fasting profound changes in the regulation of the hypothalamus-pituitary-thyroid (HPT) axis occur in order to save energy and limit catabolism. In this setting, serum T3 and T4 are decreased without an appropriate TSH and TRH response reflecting central downregulation of the HPT axis. Hepatic thyroid hormone (TH) metabolism is also affected by fasting since type 3 deiodinase (D3) is increased which is mediated by serum leptin concentrations. A recent study showed that fasting-induced changes in liver TH sulfotransferases and UDP-glucuronidases depend on a functional melanocortin system in the hypothalamus. However, the pathways connecting the hypothalamus and the liver that induce these changes are currently unknown. In the present study we investigated in rats whether the fasting-induced changes in hepatic TH metabolism are regulated by the autonomic nervous system. We selectively cut either the sympathetic (Sx) or the parasympathetic (Px) input to the liver. Serum and liver TH concentrations, deiodinase expression and activity and sulfotransferase and UDP-glucuronidase expression were measured in rats that had been fasted for 36 hours or were fed ad libitum. Fasting decreased serum T3 and T4 concentrations, while intrahepatic TH concentrations remained unchanged. D3 expression and activity increased, as was the expression of CAR, Sult1b1 and Ugt1a1, while liver D1 was unaffected. Neither sympathetic nor parasympathetic denervation affected the fasting-induced alterations. We conclude that fasting- induced changes in liver TH metabolism are not regulated via the hepatic autonomic input in a major way and more likely reflect a direct effect of humoral factors on the hepatocyte.

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