title: Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.
abstract: VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult.
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.|School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Jo E
authors.identifier: http://orcid.org/0000-0002-5722-6778
authors.initials: JE
authors.lastname: Lewis
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Brameld
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Hill
authors.affiliation: Department of Biomedical Science, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cocco
authors.affiliation: Department of Biomedical Science, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Noli
authors.affiliation: Department of Biomedical Science, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Gian-Luca
authors.initials: GL
authors.lastname: Ferri
authors.affiliation: Rowett Institute for Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Perry
authors.initials: P
authors.lastname: Barrett
authors.affiliation: School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Francis J P
authors.initials: FJ
authors.lastname: Ebling
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
authors.forename: Preeti H
authors.initials: PH
authors.lastname: Jethwa
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D004435:Eating / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000008:administration & dosage; D009479:Neuropeptides / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage; D017111:Phodopus; D051381:Rats; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C522412:TLQP-21 peptide; C522413:VGF peptide; C579141:neuroendocrine regulatory peptide-2, mouse