title: Mice that are resistant to diet-induced weight loss have greater food anticipatory activity and altered melanocortin-3 receptor (MC3R) and dopamine receptor 2 (D2) gene expression.
abstract: Diet-induced weight loss varies considerably between individuals, but the mechanisms driving these individual differences remain largely unknown. Here we investigated whether key neuropeptides involved in the regulation of energy balance or reward systems were differentially expressed in mice that were prone or resistant to caloric restriction (CR) induced weight loss. Mice (n=30 males and n=34 females) were fed 70% of their own baseline ad libitum intake for 25days, after which their brains were collected and expression of various neuropeptides were investigated and compared between the 10 male and 10 female mice that showed the greatest (high weight loss, HWL) or lowest weight loss (LWL) (n=40 in total). HWL mice showed a differential neuropeptide profile to LWL in both sexes, characterised by increased expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), leptin receptor (ObRb), and melanocortin 3 receptor (MC3R) in the arcuate nucleus. No changes in the expression of fat mass and obesity related gene (FTO) or suppressor of cytokine signalling 3 (Socs3) were observed. Levels of dopamine D2 receptor were decreased in the nucleus accumbens in HWL compared to LWL mice. HWL mice showed a stronger increase in food anticipatory activity (FAA) in response to CR than LWL mice. These results indicate that the mice prone to diet-induced weight loss experienced greater hunger, potentially driving their elevated FAA.
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK. Electronic address: l.vaanholt@abdn.ac.uk.
authors.forename: Lobke M
authors.initials: LM
authors.lastname: Vaanholt
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Mitchell
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sinclair
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: John R
authors.initials: JR
authors.lastname: Speakman
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D031204:Caloric Restriction; D004038:Diet, Reducing; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005502:Food; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy* / Q000235:genetics* / Q000378:metabolism; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D017211:Treatment Failure; D015431:Weight Loss / Q000235:genetics
chemical_list: C000600618:DRD2 protein, mouse; C470053:Mc3r protein, mouse; D009478:Neuropeptide Y; D044104:Receptor, Melanocortin, Type 3; D017448:Receptors, Dopamine D2; D054411:Receptors, Leptin
keywords: AgRP; Caloric restriction; Energy balance; FTO; Hypothalamus; Individual variability; Leptin; NPY; ObRb; POMC