Leptin: Master Regulator of Biological Functions that Affects Breathing
Bibliographic record
Abstract
Obesity is a global epidemic in developed countries accounting for many of the metabolic and cardiorespiratory morbidities that occur in adults. These morbidities include type 2 diabetes, sleep-disordered breathing (SDB), obstructive sleep apnea, chronic intermittent hypoxia, and hypertension. Leptin, produced by adipocytes, is a master regulator of metabolism and of many other biological functions including central and peripheral circuits that control breathing. By binding to receptors on cells and neurons in the brainstem, hypothalamus, and carotid body, leptin links energy and metabolism to breathing. In this comprehensive article, we review the central and peripheral locations of leptin's actions that affect cardiorespiratory responses during health and disease, with a particular focus on obesity, SDB, and its effects during early development. Obesity-induced hyperleptinemia is associated with centrally mediated hypoventilation with decrease CO2 sensitivity. On the other hand, hyperleptinemia augments peripheral chemoreflexes to hypoxia and induces sympathoexcitation. Thus, “leptin resistance” in obesity is relative. We delineate the circuits responsible for these divergent effects, including signaling pathways. We review the unique effects of leptin during development on organogenesis, feeding behavior, and cardiorespiratory responses, and how undernutrition and overnutrition during critical periods of development can lead to cardiorespiratory comorbidities in adulthood. We conclude with suggestions for future directions to improve our understanding of leptin dysregulation and associated clinical diseases and possible therapeutic targets. Lastly, we briefly discuss the yin and the yang, specifically the contribution of relative adiponectin deficiency in adults with hyperleptinemia to the development of metabolic and cardiovascular disease. © 2020 American Physiological Society. Compr Physiol 10:1047-1083, 2020.
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".