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Inter‐relation between Interleukin (IL)‐1, IL ‐6 and Body Fat Regulating Circuits of the Hypothalamic Arcuate Nucleus
Author(s) -
Schéle E.,
Benrick A.,
Grahnemo L.,
Egecioglu E.,
Anesten F.,
Pálsdóttir V.,
Jansson J.O.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12033
Subject(s) - arcuate nucleus , endocrinology , medicine , nucleus , hypothalamus , interleukin 15 , interleukin , interleukin 1β , psychology , biology , cytokine , neuroscience
Interleukin (IL)‐1 and IL ‐6 are immune modulating cytokines that also affect metabolic function because both IL ‐1 receptor I deficient ( IL ‐1 RI −/− ) 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). The present study aimed to investigate the possible mechanisms responsible 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 ‐1 RI −/− 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 the ARC , was increased in IL ‐1 RI −/− mice. The expression of NPY and agouti‐related peptide ( A g RP ), known to be co‐expressed with NPY in ARC neurones, was increased in cold exposed IL ‐6 −/− mice. IL ‐6 R α immunoreactivity was densely localised in the ARC , especially in the medial part, and was partly found in NPY positive cell bodies and also α‐ melanocyte‐stimulating hormone positive cell bodies. The expression of hypothalamic IL ‐6 was decreased in IL ‐1 RI −/− mice, whereas IL ‐1ß expression was increased in IL ‐6 −/− mice. The results of the present study 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 ‐6 R α‐like immunoreactivity is present in neurones in the medial ARC , including neurones containing NPY . Therefore, IL ‐6, IL ‐1 and NPY / A g RP could interact at the level of the hypothalamic ARC in the regulation of body fat.