title: Leptin-independent programming of adult body weight and adiposity in mice.
abstract: Low birth weight and rapid postnatal weight gain are independent and additive risk factors for the subsequent development of metabolic disease. Despite an abundance of evidence for these associations, mechanistic data are lacking. The hormone leptin has received significant interest as a potential programming factor, because differences in the profile of leptin in early life have been associated with altered susceptibility to obesity. Whether leptin alone is a critical factor for programming obesity has, until now, remained unclear. Using the leptin-deficient ob/ob mouse, we show that low birth weight followed by rapid catch-up growth during lactation (recuperated offspring) leads to a persistent increase in body weight in adult life, both in wild-type and ob/ob animals. Furthermore, recuperated offspring are hyperphagic and epididymal fat pad weights are significantly increased, reflecting greater adiposity. These results show definitively that factors other than leptin are crucial in the programming of energy homeostasis in this model and are powerful enough to alter adiposity in a genetically obese strain.
authors.affiliation: Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 OQQ, United Kingdom. ecottrell@ed.ac.uk
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Cottrell
authors.forename: Malgorzata S
authors.initials: MS
authors.lastname: Martin-Gronert
authors.forename: Denise S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.forename: Jian'an
authors.initials: J
authors.lastname: Luan
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Berends
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D004435:Eating / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D020738:Leptin; D008055:Lipids