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Göteborgs universitets publikationer

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

Författare och institution:
Erik Schéle (Institutionen för neurovetenskap och fysiologi); Anna Benrick (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Louise Grahnemo (Institutionen för neurovetenskap och fysiologi); Emil Egecioglu (Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi); Fredrik Anesten (Institutionen för neurovetenskap och fysiologi); Vilborg Palsdottir (Institutionen för neurovetenskap och fysiologi); John-Olov Jansson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Journal of neuroendocrinology, 25 ( 6 ) s. 580–589
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Obesity;NPY;IL-6 receptor α;IL-6 knockout;IL-1R1 knockout
Postens nummer:
Posten skapad:
2013-05-02 10:20
Posten ändrad:
2013-06-27 14:08

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