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Altered metabolism in RGS2 KO mice

2016· article· en· W4389007709 on OpenAlexaffabout
Katherine J. Lee, Robert Gros, Peter Chidiac

Bibliographic record

VenueThe FASEB Journal · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsWestern University
Fundersnot available
KeywordsRGS2Internal medicineEndocrinologyMetabolismRegulator of G protein signalingBiologyWild typeChemistryG proteinMedicineBiochemistryReceptorGeneGTPase-activating protein

Abstract

fetched live from OpenAlex

Regulator of G‐protein signaling 2 (RGS2) is known to inhibit Gq‐ and Gs‐mediated GPCR signalling. We have previously reported that RGS2 knock out mice (rgs2−/−) exhibit a lean phenotype compared to their wildtype (WT) counterparts, with significantly reduced fat deposits, leptin levels, and serum lipids. The objective of this study is to further elucidate the role of RGS2 in metabolism. CLAMS metabolic cages were used to measure various indices in 1 month‐, 3 month‐, and 12 month‐old rgs2−/− and WT mice. Animals were acclimatised in metabolic cages for 24 hours (12‐hour light and dark cycles), followed by another 24 hours of metabolic recordings. At both 3 months and 12 months, rgs2−/− mice displayed increased rates of respiratory intake (vO 2 ) and expiratory output (vCO 2 ), particularly during the dark cycle, suggesting increased metabolic activity in the knockouts. Furthermore, calculated respiratory exchange ratios (RER) suggest an increase in carbohydrate rather than fat or protein metabolism in rgs2−/− mice of all three age groups compared to WT. Hyperphagia, as well as increased water intake, were also observed in the knockouts at 3 and 12 months. Even with significantly increased food and water intake, 3 and 12 month‐old rgs2−/− mice maintained lower body weights compared to WT, and displayed comparable ambulatory activity. In addition, a 30% diet restriction study in which 3 month‐old mice were fed once daily, followed by metabolic cage measurements, was performed to determine possible alterations in metabolism following changes in food intake. Compared to our previous ad libitum studies, the difference in vO 2 and vCO 2 between WT and rgs2−/− mice was further exacerbated. In addition, RERs were significantly higher in rgs2−/− mice, and allude to the possibility of elevated carbohydrate metabolism in rgs2−/− mice. Ambulatory activity remained comparable to WT. Interestingly, diet restriction appears to have exacerbated the hyperphagic phenotype of rgs2−/−mice – although body weights remained stable, rgs2−/−mice consumed 50% of their daily food amounts at a 4 times higher rate than WT, and displayed hoarding behaviour. The lack of changes in overall activity between genotypes in both ad libitum and diet restricted mice suggests that weight loss in rgs2−/− mice is due to internal energy metabolism rather than overt physical activity. These results suggest that RGS2 may play an important role in the regulation of body metabolism. Support or Funding Information Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0060.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.232
Teacher spread0.220 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2016
Admission routes2
Has abstractyes

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