A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced hypothalamic inflammation

作者：Gotoh Koro^*; Inoue Megumi; Masaki Takayuki; Chiba Seiichi; Shimasaki Takanobu; Ando Hisae; Fujiwara Kansuke; Katsuragi Isao; Kakuma Tetsuya; Seike Masataka; Sakata Toshiie; Yoshimatsu Hironobu

来源：Journal of Neurochemistry, 2012, 120(5): 752-764.

DOI：10.1111/j.1471-4159.2011.07617.x

• hypothalamic inflammation
• IL-10
• Obesity
• spleen

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.

• 出版日期2012-3