DHA Increases <i>Angptl4</i> Gene Expression and Reduces LPL Activity in a PPARγ-dependent manner in Adipocytes
Bibliographic record
Abstract
Abstract Omega-3 polyunsaturated fatty acids (N-3 PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well recognized for their triacylglycerol (TAG)-lowering properties. These effects are generally attributed to reduced hepatic lipogenesis and increased β-oxidation; however, the contribution of white adipose tissue (WAT) towards the hypotriglyceridemic properties of N-3 PUFA is less defined. Lipoprotein lipase (LPL) regulates TAG hydrolysis to influence fatty acid uptake into WAT, a process that can be inhibited by angiopoietin-like 4 (ANGPTL4). When re-examining a previous mouse study, we found that mice consuming a diet rich in EPA/DHA had increased WAT Angptl4 expression in the fasted state compared to a control diet. Therefore, the goal of this study was to explore the role of N-3 PUFA on the regulation of Angptl4 expression and LPL activity in mouse adipocytes. 3T3-L1 adipocytes treated with DHA (100μM), but not ALA or EPA, increased Angptl4 expression and reduced LPL activity similar to that observed with a PPARγ agonist (pioglitazone). When Pparγ expression was knocked down with siRNA, the ability of DHA and pioglitazone to induce Angptl4 expression was ablated. Further, DHA- and pioglitazone-induced reductions in LPL activity were mitigated when Angptl4 expression was silenced. Taken together, these results suggest that DHA regulates LPL activity by increasing Angptl4 expression in a PPARγ-dependent manner. Our results have uncovered a novel mechanism by which DHA regulates ANGPTL4 to influence LPL-mediated hydrolysis of circulating TAG in adipocytes. Future in-vivo studies are necessary to determine the relevance of DHA regulation of ANGPTL4 towards whole-body lipid homeostasis and cardiometabolic health. Graphical Abstract Highlights DHA increases Angptl4 gene expression and reduces LPL activity in 3T3-L1 adipocytes Changes in FOXO1 do not explain DHA-induced changes in Angptl4 gene expression Silencing Pparγ ablates DHA-induced increases in Angptl4 gene expression Silencing Angptl4 partially attenuates DHA-induced reductions in LPL activity
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".