title: Uncoupling of peripheral and master clock gene rhythms by reversed feeding leads to an exacerbated inflammatory response after polymicrobial sepsis in mice.
abstract: Reversed feeding uncouples peripheral and master clock gene rhythms and leads to an increased risk of disease development. The aim of this study was to determine the effects of clock gene uncoupling on sepsis-induced inflammation using a mouse cecal ligation and puncture (CLP) model. C57BL/6N mice were entrained to a 12-h light-dark cycle (lights on at 7 AM). Mice were permitted ad libitum feeding either during the night (7 PM-7 AM) or the nonphysiological light phase (7 AM-7 PM) for a week before CLP. In daytime-fed mice, phase inversion of clock gene expression was observed in the liver, but not in the suprachiasmatic nucleus. Daytime-fed mice also had decreased body weight and food intake. Survival rate was significantly lower in daytime-fed mice (29%) compared with nighttime-fed mice (54%) 72 h after CLP (P = 0.03). Serum levels of interleukin 6 (IL-6), tumor necrosis factor α, high mobility group box 1, IL-1α, IL-9, eotaxin, and granulocyte colony-stimulating factor increased in daytime-fed mice compared with nighttime-fed mice after CLP. Baseline expression levels of sirtuin peroxisome 1 and proliferator-activated receptor γ coactivator 1α in the liver decreased in daytime-fed mice compared with nighttime-fed mice. Thus, daytime feeding induces clock gene uncoupling, which leads to decreased expression of longevity-related and energy metabolism proteins. Daytime feeding may also increase the levels of inflammatory cytokines, thereby increasing mortality in a mouse sepsis model. Our findings suggest that uncoupling of peripheral and master clock gene rhythms by reversed feeding exacerbates inflammatory responses.
authors.affiliation: *Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine; and †Department of Anesthesiology, Almeida Memorial Hospital, Oita, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Oyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shingu
authors.forename: Shigekiyo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D002940:Circadian Rhythm; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018805:Sepsis / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D056564:Sirtuin 1 / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1