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Interrelation between interleukin-1 (IL-1), IL-6 and body fat regulating circuits of the hypothalamic arcuate nucleus.

Artikel i vetenskaplig tidskrift
Författare Erik Schéle
Anna Benrick
Louise Grahnemo
Emil Egecioglu
Fredrik Anesten
Vilborg Palsdottir
John-Olov Jansson
Publicerad i Journal of neuroendocrinology
Volym 25
Nummer/häfte 6
Sidor 580–589
ISSN 1365-2826
Publiceringsår 2013
Publicerad vid Institutionen för neurovetenskap och fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 580–589
Språk en
Länkar dx.doi.org/10.1111/jne.12033
Ämnesord Obesity;NPY;IL-6 receptor α;IL-6 knockout;IL-1R1 knockout
Ämneskategorier Medicinska grundvetenskaper

Sammanfattning

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are immune modulating cytokines that also affect metabolic functions, as both IL-1 receptor I deficient (IL1RI -/-) and IL-6 deficient (IL-6 -/-) mice develop late-onset obesity and leptin resistance. Both IL-1 and IL-6 appear to target the central nervous system (CNS) to increase energy expenditure. The hypothalamic arcuate nucleus (ARC) is a major relay between the periphery and CNS in body fat regulation, e g by being a target of leptin. We aimed to investigate possible mechanisms for the effects exerted by endogenous IL-1 and IL-6 on body fat at the level of the ARC, as well as possible interactions between IL-1 and IL-6. Therefore, we measured the gene expression of neuropeptides of the ARC involved in energy balance in IL-1RI -/- and IL-6-/- mice. We also investigated the interactions between expression of IL-1 and IL-6 in these mice, and mapped IL-6 receptor α (IL-6Rα) in the ARC The expression of the obesity promoting peptide neuropeptide Y (NPY), found in ARC, was increased in IL-1RI -/- mice. The expression of NPY and agouti-related peptide (AgRP), known to be co-expressed with NPY in ARC neurons, was increased in cold exposed IL-6 -/- mice. IL-6Rα immunoreactivity was densely localized in the ARC, especially in the medial part, and there partly found in NPY positive cell bodies and also α-MSH positive cell bodies. The expression of hypothalamic IL-6 was decreased in IL-1RI -/- mice, while IL-1ß expression was increased in IL-6 -/- mice. The present results indicate that depletion of the activity of the fat suppressing cytokines IL-1 and IL-6 in knockout mice can increase the expression of the obesity promoting neuropeptide NPY in the ARC. Depletion of IL-1 activity suppresses IL-6 expression, and IL-6Rα -like immunoreactivity is present in neurons in the medial ARC including neurons containing NPY. Therefore, IL-6, IL-1 and NPY/AgRP could interact at the level of the hypothalamic ARC in regulation of body fat. © 2013 British Society for Neuroendocrinology.

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