title: Implication of coronin 7 in body weight regulation in humans, mice and flies.
abstract: BACKGROUND
  Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects.
  
  
  RESULTS
  We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression.
  
  
  CONCLUSIONS
  We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. anders.eriksson@neuro.uu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Eriksson
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. Michael.Williams@neuro.uu.se.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. sarah.voisin.aeris@gmail.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Voisin
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. idaehansson@gmail.com.
authors.forename: Ida
authors.initials: I
authors.lastname: Hansson
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. arunkumar.krishnan@neuro.uu.se.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. gaetan.philippot@ebc.uu.se.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Philippot
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. olga.yamskova@gmail.com.
authors.forename: Olga
authors.initials: O
authors.lastname: Yamskova
authors.affiliation: Department of Biological Sciences, University of Waikato, Hamilton, New Zealand. florence.herisson@gmail.com.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Herisson
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. rohit.dnyansagar@gmail.com.
authors.forename: Rohit
authors.initials: R
authors.lastname: Dnyansagar
authors.affiliation: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece. gmoschi@hua.gr.
authors.forename: George
authors.initials: G
authors.lastname: Moschonis
authors.affiliation: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece. manios@hua.gr.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Manios
authors.affiliation: First Department of Pediatrics, Aghia Sophia Children's Hospital, Athens University Medical School, Athens, Greece. chrousge@med.uoa.gr.
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.affiliation: Department of Biological Sciences, University of Waikato, Hamilton, New Zealand. pawel@waikato.ac.nz.
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Olszewski
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. robert.fredriksson@neuro.uu.se.
authors.forename: Robert
authors.initials: R
authors.lastname: Frediksson
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, Box 593, Uppsala, 75 124, Sweden. helgi.schioth@neuro.uu.se.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000293:Adolescent; D000818:Animals; D019167:Appetite Stimulants / Q000494:pharmacology; D001835:Body Weight / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D059305:Diet, High-Fat; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013217:Starvation / Q000378:metabolism
chemical_list: D019167:Appetite Stimulants; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C491826:Pod1 protein, Drosophila; D012333:RNA, Messenger; C072061:coronin proteins; D000431:Ethanol