title: Reverse feeding suppresses the activity of the GH axis in rats and induces a preobesogenic state.
abstract: Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P < 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4-5%; P < 0.01) and terminal liver weight (by 11%; P < 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P < 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.
authors.affiliation: Department of Endocrinology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Göteborg, Sweden.
authors.forename: Camilla A-M
authors.initials: CA
authors.lastname: Glad
authors.forename: Edward E J
authors.initials: EE
authors.lastname: Kitchen
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Russ
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Harris
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Davies
authors.forename: Evelien F
authors.initials: EF
authors.lastname: Gevers
authors.forename: Britt G
authors.initials: BG
authors.lastname: Gabrielsson
authors.forename: Timothy
authors.initials: T
authors.lastname: Wells
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000502:physiology; D054439:Ghrelin / Q000097:blood; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000254:growth & development; D008099:Liver / Q000033:anatomy & histology / Q000254:growth & development; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009929:Organ Size; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000254:growth & development; D013997:Time Factors; D015430:Weight Gain
chemical_list: D054439:Ghrelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D056926:CLOCK Proteins; C538945:Clock protein, rat