Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice

Ashley Akubuiro; M. Bridget Zimmerman; Laura L Boles Ponto; Susan A Walsh; John Sunderland; Laurie McCormick; Minati Singh

doi:10.1111/gbb.12020

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Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice

Journal article

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Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice

Ashley Akubuiro, M. Bridget Zimmerman, Laura L Boles Ponto, Susan A Walsh, John Sunderland, Laurie McCormick and Minati Singh

Genes, brain and behavior, Vol.12(3), pp.311-322

04/2013

DOI: 10.1111/gbb.12020

PMCID: PMC4589229

PMID: 23323881

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Abstract

ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [ 18 F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased mRNA expressions of ADAR2, serotonin 2C receptor (5HT 2C R), D1, D2, and mu opioid receptors and no change in CRH mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum, and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs, and hyperactive brain mesolimbic region.

overeating

Obesity

hyperactive hypothalamus

motivation and ADAR2 transgenic

Details

Title: Subtitle: Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice
Creators: Ashley Akubuiro - Internal Medicine, University of Iowa, Iowa City, IA-52246
M. Bridget Zimmerman - Internal Medicine, University of Iowa, Iowa City, IA-52246
Laura L Boles Ponto - Internal Medicine, University of Iowa, Iowa City, IA-52246
Susan A Walsh - Internal Medicine, University of Iowa, Iowa City, IA-52246
John Sunderland - Internal Medicine, University of Iowa, Iowa City, IA-52246
Laurie McCormick - Internal Medicine, University of Iowa, Iowa City, IA-52246
Minati Singh - Internal Medicine, University of Iowa, Iowa City, IA-52246
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.12(3), pp.311-322
DOI: 10.1111/gbb.12020
PMID: 23323881
PMCID: PMC4589229
NLM abbreviation: Genes Brain Behav
ISSN: 1601-1848
eISSN: 1601-183X
Language: English
Date published: 04/2013
Academic Unit: Radiology; Psychiatry; Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Physics and Astronomy; Radiation Oncology; Internal Medicine
Record Identifier: 9983997467902771

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