Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-Aged Mice to Diet-Induced Insulin Resistance
Bibliographic record
Abstract
OBJECTIVE: Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal muscle fatty acid handling and to determine how this contributes to the development of diet-induced insulin resistance. RESEARCH DESIGN AND METHODS: Whole-body and skeletal muscle insulin resistance were studied in young and middle-aged wild-type and CD36 knockout (KO) mice fed either a standard or a high-fat diet for 12 weeks. Molecular signaling pathways, intramuscular triglycerides accumulation, and targeted metabolomics of in vivo mitochondrial substrate flux were also analyzed in the skeletal muscle of mice of all ages. RESULTS: Middle-aged mice fed a standard diet demonstrated an increase in intramuscular triglycerides without a concomitant increase in insulin resistance. However, middle-aged mice fed a high-fat diet were more susceptible to the development of insulin resistance-a condition that could be prevented by limiting skeletal muscle fatty acid transport and excessive lipid accumulation in middle-aged CD36 KO mice. CONCLUSION: Our data provide insight into the mechanisms by which aging becomes a risk factor for the development of insulin resistance. Our data also demonstrate that limiting skeletal muscle fatty acid transport is an effective approach for delaying the development of age-associated insulin resistance and metabolic disease during exposure to a high-fat diet.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.000 | 0.000 |
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 teacher head, 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".