Neither Linoleic Acid nor Arachidonic Acid Promote White Adipose Tissue Inflammation in <i>Fads2−/−</i> Mice Fed Low Fat Diets
Bibliographic record
Abstract
Dietary n‐6 polyunsaturated fatty acids (PUFAs) are widely perceived to promote inflammation and contribute to the development of cardiometabolic disease. However, emerging evidence casts doubt on the relationship between n‐6 PUFAs and inflammation, and suggests that different n‐6 PUFAs may influence this relationship differently. Establishing the roles of individual n‐6 PUFAs in vivo is challenging because linoleic acid (LA, 18:2n6) is endogenously and continuously converted into arachidonic acid (AA, 20:4n6). The fatty acid desaturase 2 gene ( Fads2 ) encodes the rate‐limiting delta‐6 desaturase enzyme necessary for converting LA into AA. The goal of this study was to elucidate the independent effects of the two predominant dietary n‐6 PUFAs, LA and AA, on inflammatory signalling in white adipose tissue (WAT) using Fads2 knockout ( Fads2 −/−) mice. We hypothesized that LA would not induce WAT inflammation unless it is converted into AA. Male C57BL/6 wild‐type (WT) and Fads2 −/− mice (n=8 per diet per genotype group) were fed low‐fat isocaloric diets containing either 7% corn oil w/w (containing ~42% LA) or 7% ARASCO oil w/w (containing ~27% AA) for 9 weeks. WAT gene expression, protein levels, and triacylglycerol (TAG) fatty acid composition were analyzed by qRT‐PCR, Western blots, and gas chromatography, respectively. Fads2 −/− mice fed the corn diet had no downstream AA, and reduced GLA (18:3n6) and DGLA (20:3n6), in TAGs compared to their WT counterparts. WT and Fads2 −/− mice fed the ARASCO diet had significantly higher levels of AA, DGLA, and GLA in TAGs compared to WT mice fed the corn diet. Estimated delta‐5 desaturase enzyme activity (AA: DGLA ratio) in WAT was reduced in Fads2 −/− mice fed the corn diet compared to their WT counterparts (p<0.05), and this was reflected by a 1.6‐fold reduction in FADS1 protein content (p<0.04). No differences in gene expression for common cytokines (e.g. Mcp‐1, Ccl5, Arg1, Nos2 ) and key regulators of oxylipin production (e.g. Cox‐2, Alox12, Alox15 ) were detected between WT and Fads2 −/− mice fed either diet. WT and Fads2 −/− mice fed both corn and ARASCO diets showed no difference in total or phosphorylated STAT3 and p38 proteins. These results suggest that in an unstimulated model neither LA nor AA promote WAT inflammation when consumed as part of a low‐fat diet. Support or Funding Information This work was supported by a grant from NSERC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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.
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 source (direct Gemma or distilled Codex), 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".