LPS immune challenge reduces arcuate nucleus TSHR and CART mRNA and elevates plasma CART peptides

• Main Authors: Jonathan R. Burgos, Britt-Marie Iresjö, Linda Olsson, Ulrika Smedh
• Format: Article
• Language: English
• Published: BMC 2019-12-01
• Series: BMC Neuroscience
• Subjects: Arcuate nucleus; Paraventricular nucleus; Cocaine- and amphetamine-regulated transcript; Thyrotropin; Lipopolysaccharide
• Online Access: https://doi.org/10.1186/s12868-019-0539-z

Abstract Background The aim was to examine the impact of lipopolysaccharide-induced systemic inflammation on expression of mRNA for cocaine- and amphetamine-regulated transcript (CART) and the thyrotropin receptor (TSHR) and its ligands in CNS areas of relevance for feeding controls and metabolism. Lipopolysaccharide effects on plasma levels of TSH and CART peptides were also examined. Methods Lipopolysaccharide (150–200 μg/mouse) was injected in C57BL/6J mice and tissue and plasma samples taken after 24 h. To establish if plasma increase in CART peptide levels were prostanoid dependent, indomethacin was given via the drinking water beginning 48 h prior to LPS. We evaluated mRNA expression for CART, TSHR, TSHβ, and thyrostimulin in brain and pituitary extracts. Plasma levels of TSH, CARTp, and serum amyloid P component were analyzed by ELISA. Results Lipopolysaccharide suppressed TSHR mRNA expression in the arcuate nucleus and the pituitary. CART mRNA expression was reduced in the arcuate nucleus but elevated in the pituitary of mice treated with Lipopolysaccharide, whereas plasma TSH remained unchanged. Plasma CART peptide concentration increased after LPS treatment in a prostanoid-independent manner, and CART peptide levels correlated positively to degree of inflammation. Conclusions Our findings suggest that central and peripheral CART is affected by acute inflammation. Considering the role of the arcuate nucleus in feeding controls, our data highlight TSHR and CART as putative neuroendocrine signaling components that respond to inflammation, perhaps to maintain weight and metabolic homeostasis during states of disease.