AAV-mediated gene transfer of the obesity-associated gene Etv5 in rat midbrain does not affect energy balance or motivated behavior.
Several genome-wide association studies have implicated the transcription factor E-twenty- six version 5 (Etv5) in the regulation of body mass index. Further substantiating the role of Etv5 in feeding behavior are the findings that targeted disruption of Etv5 in mice leads to decreased body weight gain and that expression of Etv5 is decreased in the ventral tegmental area and substantia nigra pars compacta (VTA/SNpc) after food restriction. As Etv5 has been suggested to influence dopaminergic neurotransmission by driving the expression of genes that are responsible for the synthesis and release of dopamine, we investigated if expression levels of Etv5 are dependent on nutritional state and subsequently influence the expression levels of tyrosine hydroxylase. While it was shown that Etv5 expression in the VTA/SNpc increases after central administration of leptin and that Etv5 was able to drive expression of tyrosine hydroxylase in vitro, AAV-mediated gene transfer of Etv5 into the VTA/SNpc of rats did not alter expression of tyrosine hydroxylase in vivo. Moreover, AAV-mediated gene transfer of Etv5 in the VTA/SNpc did not affect measures of energy balance or performances in a progressive ratio schedule. Thus, these data do not support a role for increased expression of Etv5 in the VTA/SNpc in the regulation of feeding behavior.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Arjen J
AJ
Boender
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Nivard A
NA
Koning
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
José K
JK
van den Heuvel
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Mieneke C M
MC
Luijendijk
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Andrea J
AJ
van Rozen
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Susanne E
SE
la Fleur
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Roger A H
RA
Adan
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism* / Q000502:physiology; D009042:Motivation / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D065842:Pars Compacta / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; C513243:Etv5 protein, rat; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase