Sexually dimorphic effects of angiopoietin-like 2 on energy metabolism and hypothalamic neuropeptide regulation
Bibliographic record
Abstract
BACKGROUND: Adipokines regulate body weight and metabolism by targeting the hypothalamus, influencing feeding, energy expenditure (EE) and insulin sensitivity. Angiopoietin-like 2 (Angptl2) is a pro-inflammatory adipokine linking obesity to insulin resistance. Both Angptl2 and its receptor are expressed in the central nervous system. Yet, the contribution of Angptl2 to the regulation of energy metabolism and relevant hypothalamic neuropeptides in male and female mice is unknown. We aim at determining the impact of Angptl2 knockdown (KD) on energy balance, nutrient partitioning and hypothalamic responses to a standard (STD) or high-fat diet (HFD) in mice. METHODS: Three-month-old male and female Angptl2-KD mice and wildtype (WT) littermates were fed 16 weeks either a STD or a HFD. Body weight, food consumption and insulin sensitivity were assessed along with measurements of EE, respiratory exchange ratio (RER) and locomotor activity. We quantified the expression of Angptl2 and its receptors itga5, mag and pirb in the medio-basal hypothalamus (MBH) of WT mice, and MBH neuropeptide Y (NPY), agouti-related neuropeptide (AgRP) and proopiomelanocortin (POMC) gene expression in both KD and control fasting mice. RESULTS: Lack of Angptl2 reduced food intake in males on both diets, and in females on HFD. In KD males, this anorexigenic effect was associated with lower body weight, increased EE, improved insulin sensitivity and lower hypothalamic orexigenic NPY expression compared to controls. Female Angptl2-KD mice however, exhibited unaltered body weight, EE and insulin sensitivity, and elevated NPY, AgRP and MC4R expression compared to controls. Fasting caused an increase in the MBH of mag expression in males and females but Angptl2 expression only in female mice. CONCLUSIONS: Angptl2 KD improved diet-induced obesity and associated metabolic dysfunction in male mice. The lack of similar changes in female mice and divergent MBH neuropeptide profile suggest that sex-dependent mechanisms underly the anabolic effects of this proinflammatory adipokine.
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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 | 0.000 |
| 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) | 0.003 | 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 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".