Knockdown of angiopoietin‐like 2 mimics the benefits of intermittent fasting on weight loss and insulin sensitivity in mice
Bibliographic record
Abstract
Obesity and elevated body fat are generally associated with a higher risk of metabolic diseases such as type 2 diabetes, but the mechanisms involved are not clear. Angiopoietin‐like 2 (ANGPTL2), a circulating pro‐inflammatory glycoprotein mainly secreted by adipose tissues, is now considered as a key mediator linking obesity to insulin resistance. Accordingly, high levels of ANGPTL2 in humans are associated with obesity and the development of diabetes, and in Angptl2 −/− mice exposed to a high fat diet, body fat is lower and insulin sensitivity better than in wild‐type (WT) mice. Various approaches have been developed to promote weight loss and increase insulin sensitivity such as intermittent fasting, an efficient but strenuous lifestyle intervention that involves alternating cycles of fasting and eating. Our objective was to investigate whether the knockdown of ANGPTL2 in mice reproduces or improves the benefits of intermittent fasting in WT mice on weight and insulin sensitivity. Intermittent fasting (one day of fasting/one day of free access to food) for 4 months reduced (p<0.05) Angptl2 mRNA expression by 53% in adipose tissue from WT mice. Both intermittent fasting for 4 months and knockdown of ANGPTL2 similarly decreased (p<0.05) feeding efficiency by 55%, weight gain by 55%, liver (38%) and adipose (around 55%) tissue weights and similarly increased (p<0.05) insulin sensitivity (measured by the insulin tolerance test). All measured parameters were similar between WT mice fed with an intermittent fasting regimen and ANGPTL2 knockdown mice fed ad libitum , suggesting that knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight loss and insulin sensitivity. Finally, intermittent fasting in ANGPTL2 knockdown mice did not further reduce weight gain, adipose tissue and liver weight, and did not further improve insulin sensitivity. We therefore propose that lowering ANGPTL2 could be a useful and promising strategy to limit obesity and prevent insulin resistance. The development of pharmacological inhibitors of ANGTPL2 is needed. Support or Funding Information Canadian Institutes of Health Research
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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) | 0.001 | 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 | 0.001 | 0.002 |
| 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".