Altered Fatty Acid and Mitochondrial Metabolism in the Liver of Pregnant Adiponectin‐Deficient Mice Contributes to Insulin Resistance and Gestational Diabetes Mellitus
Bibliographic record
Abstract
Introduction Gestational diabetes mellitus (GDM) is a common pregnancy‐related health condition. While genetics, lifestyle and diet contribute to development of GDM, evidence suggests that low levels of adiponectin increases the risk for GDM. Adiponectin is a fat derived hormone that improves the sensitivity of tissues to insulin. We hypothesize that adiponectin deficiency causes fatty liver during pregnancy, ultimately contributing to the development of GDM. Methods We compared the glucose and insulin tolerance of pregnant (3 rd trimester) adiponectin−/− (strain B6;129‐ Adipoq tm1Chan /J) and wild‐type mice, and assessed parameters of hepatic metabolism, including mitochondrial function and fatty acid metabolism. We assessed the impact of adiponectin supplementation by administering adenovirus mediated full length adiponectin at the end of the second trimester of pregnancy, and comparing to control containing GFP. Results In the third trimester, pregnant adiponectin−/− mice exhibited fasting hyperglycemia regardless of diet (9.2mmol/L vs. 7.7mmol/L in controls, p<0.05). These mice display impaired glucose and insulin tolerance relative to wild‐type controls. Pregnant adiponectin−/− mice develop hepatic steatosis, including a 3‐fold elevation in hepatic triglycerides (p<0.05). This was associated with altered hepatic lipid metabolism, including a 2.5 fold increase in fatty acid synthase expression (p<0.05), elevated circulating free fatty acids, triglycerides and cholesterol. Nearly 2‐fold reduction (p<0.05) in maximal mitochondrial respiration was observed via oxidative flux analyzer in hepatocytes of adiponectin −/− mice. Hepatocytes from pregnant adiponectin−/− mice show dramatically reduced respiratory capacity when using fatty acids alone, and display elevated synthesis and secretion of triglycerides and cholesterol. Gestational weight gain and food consumption were similar in knockout and wild‐type mice. Adiponectin supplementation to pregnant adiponectin−/− mice significantly improved glucose tolerance, prevented fasting hyperglycemia, and attenuated fatty liver development. Conclusion Results show that adiponectin deficiency is associated with altered hepatic lipid metabolism and hepatic steatosis during pregnancy. Consequently, adiponectin deficiency contributes to mid‐gestation insulin resistance and hyperglycemia characteristic of GDM. Moreover, adiponectin supplementation rescues the effects of adiponectin deficiency on insulin sensitivity and hepatic lipid metabolism. Support or Funding Information Research Manitoba, Children's Hospital Research Institute of Manitoba
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".