Estrogen‐Related Receptor α (ERRα) represses PGC‐1α‐activated PEPCK gene transcription
Bibliographic record
Abstract
The orphan nuclear receptor ERRα acts as a downstream effector of the transcriptional coactivator PGC‐1α in the induction of genes important for mitochondrial oxidative metabolism. PGC‐1α is also known as a potent activator of the transcriptional program required for hepatic gluconeogenesis, and in particular of the key gluconeogenic enzyme PEPCK. We report here that ERRα binding to the PEPCK gene promoter leads to the repression of PEPCK expression. Gain‐ and loss‐of function studies suggest that ERRα at the PEPCK promoter antagonizes the recruitment and stimulatory action of PGC‐1α. Consistent with these findings, animals that lack ERRα show increased expression of gluconeogenic genes, including PEPCK and glycerol kinase, but decreased expression of mitochondrial genes. We conclude that ERRα has opposing effects on genes important for mitochondrial oxidative capacity and for gluconeogenesis. Decreased mitochondrial oxidative function and increased gluconeogenesis are associated with diabetes. The different functions of ERRα in the regulation of these pathways suggest that increased ERRα activity may exert beneficial effects in diabetic subjects by two distinct mechanisms: enhancing mitochondrial oxidative capacity in peripheral tissues and liver, and suppressing hepatic glucose production.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 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".