title: A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced hypothalamic inflammation.
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.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Oita University, Hasama, Yufu, Japan. gotokoro@med.oita-u.ac.jp
authors.forename: Koro
authors.initials: K
authors.lastname: Gotoh
authors.forename: Megumi
authors.initials: M
authors.lastname: Inoue
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Hisae
authors.initials: H
authors.lastname: Ando
authors.forename: Kansuke
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Isao
authors.initials: I
authors.lastname: Katsuragi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kakuma
authors.forename: Masataka
authors.initials: M
authors.lastname: Seike
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology*; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000172:deficiency / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000209:etiology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D013156:Splenectomy / Q000379:methods; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D000447:Aldehydes; D016207:Cytokines; D009478:Neuropeptide Y; D016753:Interleukin-10; D000521:alpha-MSH; C027576:4-hydroxy-2-nonenal