title: Weight cycling promotes fat gain and altered clock gene expression in adipose tissue in C57BL/6J mice.
abstract: Repeated attempts to lose weight by temporary dieting may result in weight cycling, eventually further gain of body fat, and possible metabolic adaptation. We tested this with a controlled experiment in C57BL/6J mice subjected to four weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding (LF). To search for genes involved in an adaptive mechanism to former weight cycling and avoid acute effects of the last cycle, the last hypercaloric feeding period was prolonged by an additional 2 wk before euthanization. Total energy intake was identical in WC and HF. However, compared with HF, the WC mice gained significantly more total body mass and fat mass and showed increased levels of circulating leptin and lipids in liver. Both the HF and WC groups showed increased adipocyte size and insulin resistance. Despite these effects, we also observed an interesting maintenance of circulating adiponectin and free fatty acid levels after WC, whereas changes in these parameters were observed in HF mice. Global gene expression was analyzed by microarrays. Weight-cycled mice were characterized by a downregulation of several clock genes (Dbp, Tef, Per1, Per2, Per3, and Nr1d2) in adipose tissues, which was confirmed by quantitative PCR. In 3T3-L1 cells, we found reduced expression of Dbp and Tef early in adipogenic differentiation, which was mediated via cAMP-dependent signaling. Our data suggest that clock genes in adipose tissue may play a role in metabolic adaptation to weight cycling.
authors.affiliation: Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway;
authors.forename: S N
authors.initials: SN
authors.lastname: Dankel
authors.forename: E M
authors.initials: EM
authors.lastname: Degerud
authors.forename: K
authors.initials: K
authors.lastname: Borkowski
authors.forename: E
authors.initials: E
authors.lastname: Fjære
authors.forename: L K
authors.initials: LK
authors.lastname: Midtbø
authors.forename: C
authors.initials: C
authors.lastname: Haugen
authors.forename: M H
authors.initials: MH
authors.lastname: Solsvik
authors.forename: A M
authors.initials: AM
authors.lastname: Lavigne
authors.forename: B
authors.initials: B
authors.lastname: Liaset
authors.forename: J V
authors.initials: JV
authors.lastname: Sagen
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
authors.forename: G
authors.initials: G
authors.lastname: Mellgren
authors.forename: L
authors.initials: L
authors.lastname: Madsen
mesh_terms: D041721:3T3-L1 Cells; D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D031204:Caloric Restriction / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: adipokines; caloric restriction; clock genes; metabolism; obesity