Τίτλος:
Implication of coronin 7 in body weight regulation in humans, mice and
flies
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Conclusion: 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.
Συγγραφείς:
Eriksson, Anders
Williams, Michael J.
Voisin, Sarah
Hansson,
Ida
Krishnan, Arunkumar
Philippot, Gaetan
Yamskova, Olga and
Herisson, Florence M.
Dnyansagar, Rohit
Moschonis, George and
Manios, Yannis
Chrousos, George P.
Olszewski, Pawel K. and
Frediksson, Robert
Schioth, Helgi B.
Περιοδικό:
BMC Neuroscience
Λέξεις-κλειδιά:
Coronin 7; Obesity; Homeostatic control; Gene expression
DOI:
10.1186/s12868-015-0151-9