FNDC5: A novel player in metabolism and metabolic syndrome
Bibliographic record
Abstract
Half a decade ago, transmembrane protein fibronectin type III domain-containing protein 5 (FNDC5) was found to be cleaved as a novel myokine irisin, which burst into prominence for browning of white adipose tissue during exercise. However, FNDC5, the precursor of irisin, has been paid relatively little attention compared with irisin despite evidence that FNDC5 is associated with the metabolic syndrome, which accounts for one-fourth of the world's adult population and contributes to diabetes, cardiovascular disease and all-cause mortality. Besides N-terminal and C-terminal sequences, the FNDC5 protein contains an irisin domain and a short transmembrane region. FNDC5 has shown to be widely distribute in different tissues and is highly expressed in heart, brain, liver, and skeletal muscle. Clinical studies have demonstrated that FNDC5 is essential for maintaining metabolic homeostasis and dysregulation of FNDC5 will lead to systemic metabolism imbalance and the onset of metabolic disorders. Growing evidence has suggested that FNDC5 gene polymorphisms are related to health and disease in different human populations. Additionally, FNDC5 has been found relevant to the regulation of metabolism and metabolic syndrome through diverse upstream and downstream signaling pathways in experimental studies. The present review summarizes the characteristics, clinical significance, and molecular mechanisms of FNDC5 in metabolic syndrome and proposes a novel concept that FNDC5 is activated by forming a putative ligand-receptor complex. Knowledge about the role of FNDC5 may be translated into drug development and clinical applications for the treatment of metabolic disorders.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".