Highly palatable diet changes brain glucose metabolism in mice
Bibliographic record
Abstract
Abstract Background Obesity has become a global public health issue and is knowingly associated with several pathological conditions. Epidemiological data indicate it is an important risk factor for the development of neurodegenerative diseases, such as Alzheimer’s Disease (AD). However, the pathological mechanisms connecting these two conditions are still elusive. Current evidence points toward glucose metabolism dysregulation, as well as defective insulin signaling and low grade inflammation. Objective: Our main goal was to investigate the effects of a highly palatable diet (HPD) on brain glucose metabolism. Hypothesis: We hypothesized that the obesity induced by the HPD could lead to alterations in brain glucose metabolism similar to those found in AD. Methods Male C57BL/6J mice (45 days old) were fed with HPD (rich in simple sugars and fat) for four months. They were then examined in vivo via microPET [18F]FDG. Data from images were used to assemble [18F]FDG‐derived brain metabolic networks. A glucose tolerance test (GTT) was also performed to assess peripheral insulin response. Post‐mortem, the brain tissue was used in a high resolution respirometry test to evaluate mitochondrial activity. Results HPD animals presented increased body weight (HPD= 37.17±4.38g; control= 28.72±1.23g; P<0.0001) and abnormal peripheral tolerance to glucose (peak blood glucose: HPD=421.93±47.13mg/dL; control=323.60±43.83mg/dL P<0.0001). HPD also induced [18F]FDG hypermetabolism in the prefrontal cortex and a hypersynchronicity in the metabolic network, where the hypothalamus appears to be more connected to the hippocampus, thalamus, prefrontal cortex, and striatum. Brain post mortem analysis indicated a less efficient mitochondrial oxidative phosphorylation in the hypothalamus of HPD fed animals as measured by the Respiratory Chain Ratio (HPD=0.640±0.022; control= 0.810±0.012 P<0.001). Conclusion These preliminary results show that HPD causes peripheral and central disturbances in glucose metabolism, also altering brain mitochondrial activity. Interestingly, in vivo imaging indicates that the prefrontal cortex is highly active and the hypothalamus is unusually connected to other brain regions in these animals.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".