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A novel anti‐inflammatory role for spleen‐derived interleukin‐10 in obesity‐induced hypothalamic inflammation
Author(s) -
Gotoh Koro,
Inoue Megumi,
Masaki Takayuki,
Chiba Seiichi,
Shimasaki Takanobu,
Ando Hisae,
Fujiwara Kansuke,
Katsuragi Isao,
Kakuma Tetsuya,
Seike Masataka,
Sakata Toshiie,
Yoshimatsu Hironobu
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07617.x
Subject(s) - inflammation , medicine , endocrinology , spleen , hypothalamus , cytokine , obesity , systemic inflammation , pathogenesis , interleukin , interleukin 10 , immunology
J. Neurochem. (2012) 120 , 752–764. Abstract Obesity can be associated with systemic low‐grade inflammation that contributes to obesity‐related metabolic disorders. Recent studies raise the possibility that hypothalamic inflammation contributes to the pathogenesis of diet‐induced obesity (DIO), while another study reported that obesity decreases the expression of pro‐inflammatory cytokines in spleen. The following study examines the hypothesis that obesity suppresses the splenic synthesis of the anti‐inflammatory cytokine, interleukin (IL)‐10, thereby resulting in chronic hypothalamic inflammation. The results showed that due to oxidative stress or apoptosis, the synthesis of splenic IL‐10 was decreased in DIO when compared with non‐obesity rats. Splenectomy (SPX) accelerated DIO‐induced inflammatory responses in the hypothalamus. Interestingly, SPX suppressed the DIO‐induced increases in food intake and body weight and led to a hypothalamic pro‐inflammatory state that was similar to that produced by DIO, indicating that hypothalamic inflammation exerts a dual effect on energy metabolism. These SPX‐induced changes were inhibited by the systemic administration of IL‐10. Moreover, SPX had no effect on hypothalamic inflammatory responses in IL‐10‐deficient mice. These data suggest that spleen‐derived IL‐10 plays an important role in the prevention of hypothalamic inflammation and may be a therapeutic target for the treatment of obesity and hypothalamic inflammation.