Metabolic responses to intermittent hypoxia are regulated by sex and gonadal hormones in mice.
Bibliographic record
Abstract
Sleep apnea is a respiratory disease characterized by intermittent hypoxia (IH) due to repeated obstructions of the airways during sleep. Men and women after menopause are more likely to develop sleep apnea than women before menopause. In addition to disrupting sleep quality, sleep apnea is strongly associated with metabolic syndrome and type 2 diabetes, and the metabolic consequences of sleep apnea may vary according to sex or the hormonal status. We therefore used intact males, intact females, and ovariectomized (OVX) female mice to ask if IH induces sex‐specific metabolic responses and if endogenous female hormones prevent these effects. Within each group, mice were exposed to room air (RA) or IH (nadir 6% O 2 , 10 cycles/hour, 12 hours/day) during 2 weeks. Body weights were measured before and after the exposures to IH. At the end of the IH exposures, mice were fasted for 6 hours, a blood sample was drawn from the saphenous vein to measure fasting plasma glucose and insulin levels. We then performed intraperitoneal insulin or glucose tolerance tests to further assess glucose homeostasis. In distinct groups, we assessed liver levels of glycogen, triglycerides (TG), and expression levels of selected genes involved in glucose metabolism. In intact males, IH reduced weight gain, lowered the fasting levels of glucose and insulin in plasma, and slightly increased glucose tolerance. In intact females, the only effect of IH was a modest decrease of glucose tolerance. In OVX females, IH exposures reduced fasting glucose and insulin levels, induced insulin resistance, and led to a major glucose intolerance. In the liver, IH exposures slightly increased glycogen levels in males and OVX females and had a profound effect to decrease TG levels only in males. The expression levels of key liver glycolytic (LDH) and mitochondrial (Citrate synthase, PDH, PDK) genes were reduced by IH in males or in OVX females. We conclude that the metabolic consequences of IH exposures are sex specific. In females, endogenous ovarian hormones appear to prevent the development of a major glucose intolerance during IH exposure and help maintaining a normal expression pattern of hepatic genes involved in glucose metabolism. Surprisingly, the effects of IH are different in males and OVX females, suggesting that endogenous testosterone might also have a role in males. Support or Funding Information Supported by CIHR.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".