Investigating the role of the gut in fructose induced glucose intolerance
Bibliographic record
Abstract
Background: Obesity and type 2 diabetes (T2D) are global health challenges linked to the consumption of ultra processed foods high in sucrose. The latter sugar is one key source of excess dietary fructose. Although evidence indicates that excess fructose can negatively impact metabolic health and blood glucose regulation, the mechanisms are ill-defined. Excess dietary fructose overwhelms enterocyte absorption in the small intestine and spills over the distal gut. Interestingly, excess fructose has been linked to an expansion of the gut's absorptive surface and increased fat absorption. However, it remains uncertain whether excess dietary fructose impairs glucose tolerance by increasing gut absorptive surface and gut glucose absorption (GGA). Aims and Hypothesis: We hypothesized that dietary fructose impairs glucose tolerance by expanding gut surface and upregulating glucose transport machinery, which promotes increased GGA and glucose intolerance. We aim to (i) map the onset of altered glucose tolerance, plasma insulin, and altered GGA in mice fed a high-fructose diet, and (ii) investigate whether fructose driven increase in GGA correlates with an expansion of absorptive surface. Methodology: C57BL6J male mice were fed a high-sucrose (HS, with 8.5 %Kcal fructose) or a sucrose-free (CTL) diet. Oral glucose tolerance tests (OGTT) and 3-O-methyl-glucose (3-OMG) tests were conducted at weeks 1, 4, and 7 weeks after introduction of diets. Results: We found that 4 weeks, but not 1 week, on HS diet is suffcient to cause glucose intolerance, which persists, but is not aggravated, at week 7. Interestingly, HS-mice did not become insulin resistant, as revealed by plasma insulin levels, homa-ir, and insulin resistance index comparable to that of CTL-mice. HS-fed mice had longer small intestines than CTL-fed counterparts, which is indicative of increased absorptive surface. Furthermore, HS-fed mice presented higher plasma 3-OMG than CTL-mice at weeks 4 and 7, but not at week 1, indicating higher GGA that parallels the trajectory of deteriorated glucose tolerance. Conclusion: Changes in GGA and gut surface are early fructose-induced manifestations relevant to blood glucose control. We will next assess the expression of glucose transporters and perform morphometric analysis in the small intestine of these mice. We will also analyze how gut microbial populations correlate with fructose-induced changes to gut homeostasis. This study uncovers novel mechanisms by which dietary fructose contributes to impaired blood glucose control and elevates the risk of T2D. The findings from this work will lay the groundwork for novel approaches to address the growing burden of metabolic disorders worldwide. Laval university, CRIUCPQ, Fonds de recherche santé Québec. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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) | 0.000 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".