Global Inactivation of the Pla2g6 Gene in Mice Does Not Cause Dyslipidemia under Chow or High-fat Diet Conditions
Bibliographic record
Abstract
BACKGROUND: Genome-wide association studies suggest that plasma triacylglyceride (TAG) in humans was associated with variation in the PLA2G6 locus, a gene that encodes calcium-independent phospholipase A2 (iPLA2 β). The objective of the present study is to understand the impact of genetic inactivation of iPLA2 β on hepatic TAG metabolism in C57BL/6 mice. METHODS: Male iPLA2 β (+) (/-) mice were backcrossed with female iPLA2 β (-/-) mice for up to 10 generations prior to experiments. Lipid and lipoprotein metabolism from plasma, hepatocytes, thigh subcutaneous adipose and thigh skeletal muscle tissues of the mice were determined under various experimental conditions. RESULTS: The iPLA2 β (-/-) mice, either male or female as compared with iPLA2 β (+) (/) (+) littermates, showed no change in fasted or postprandial plasma TAG or total cholesterol at young (12-15 weeks) or old (40-44 weeks) ages under chow diet or high-fat diet (HFD) conditions. However, fractionation of plasma lipoproteins showed that under HFD conditions, there was a significant increase (by 40%) in apoB-100 association with VLDL1 fractions in iPLA2 β (-/-) mice as compared with iPLA2 β (+) (/) (+) littermates. There was no significant difference in triglyceride or cholesterol contents in the liver, muscle, or adipose tissue between iPLA2 β (-/-) and iPLA2 β (+/+) littermates. Metabolic labeling experiments with cultured primary hepatocytes isolated from iPLA2 β (-/-) mice also showed 2-fold increase in the secretion of [(35)S]methionine-labeled apoB-100 in VLDL1 fractions as compared with that from iPLA2 β (+) (/) (+) hepatocytes. Likewise, secretion of [(3)H]palmitate-labeled TAG from the iPLA2 β (-/-) hepatocytes was increased by 2-fold. CONCLUSIONS: Although iPLA2 β may play a role in TAG-rich VLDL1 production from cultured hepatocytes, there is no evidence that inactivation of iPLA2 β would lead to dyslipidemia in mice in vivo.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".