title: Repletion of TNFα or leptin in calorically restricted mice suppresses post-restriction hyperphagia.
abstract: The causes of post-restriction hyperphagia (PRH) represent a target for drug-based therapies to prevent obesity. However, the factors causing PRH are poorly understood. We show that, in mice, the extent of PRH was independent of the time under restriction, but depended on its severity, suggesting that PRH was driven by signals from altered body composition. Signals related to fat mass were important drivers. Circulating levels of leptin and TNFα were significantly depleted following caloric restriction (CR). We experimentally repleted their levels to match those of controls, and found that in both treatment groups the level of PRH was significantly blunted. These data establish a role for TNFα and leptin in the non-pathological regulation of energy homeostasis. Signals from adipose tissue, including but not limited to leptin and TNFα, regulate PRH and might be targets for therapies that support people engaged in CR to reduce obesity.
authors.affiliation: Aberdeen Centre for Energy Regulation and Obesity, Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen AB21 9SB, Scotland, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hambly
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Zoë A
authors.initials: ZA
authors.lastname: Archer
authors.forename: Kim M
authors.initials: KM
authors.lastname: Moar
authors.forename: Julian G
authors.initials: JG
authors.lastname: Mercer
authors.forename: John R
authors.initials: JR
authors.lastname: Speakman
mesh_terms: D050154:Adiposity; D000818:Animals; D001823:Body Composition; D031204:Caloric Restriction; D004032:Diet; D005786:Gene Expression Regulation; D006963:Hyperphagia / Q000097:blood* / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood*; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D020738:Leptin; D014409:Tumor Necrosis Factor-alpha