title: Snord116 is critical in the regulation of food intake and body weight.
abstract: Prader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans. Recent clinical reports have suggested that micro-deletion of the Snord116 gene cluster can lead to PWS, however, the extent of the contributions of the encoded snoRNAs is unknown. Here we show that mice lacking Snord116 globally have low birth weight, increased body weight gain, energy expenditure and hyperphagia. Consistent with this, microarray analysis of hypothalamic gene expression revealed a significant alteration in feeding related pathways that was also confirmed by in situ hybridisation. Importantly, selective deletion of Snord116 only from NPY expressing neurons mimics almost exactly the global deletion phenotype including the persistent low birth weight, increased body weight gain in early adulthood, increased energy expenditure and hyperphagia. Mechanistically, the lack of Snord116 in NPY neurons leads to the upregulation of NPY mRNA consistent with the hyperphagic phenotype and suggests a critical role of Snord116 in the control of NPY neuronal functions that might be dysregulated in PWS.
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Purtell
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Fu
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Lee
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Aepler
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.affiliation: Bone Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Ronaldo F
authors.initials: RF
authors.lastname: Enriquez
authors.affiliation: Bone Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.affiliation: Department of Pediatrics, College of Medicine, Center for Smell and Taste, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Zolotukhin
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Lesley V
authors.initials: LV
authors.lastname: Campbell
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.|School of Medical Sciences, University of NSW, NSW, Australia.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
mesh_terms: D000818:Animals; D001069:Appetite Regulation; D001823:Body Composition; D001835:Body Weight; D050260:Carbohydrate Metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D020537:RNA, Small Nucleolar; C000609194:SNORD116 RNA, mouse