A314 INTESTINAL EPITHELIAL SPECIFIC DELETION OF HNF4α PREVENTS OBESITY IN HIGH-FAT DIET FED MICE WITHOUT AFFECTING INTESTINAL UPTAKE OF FATTY ACIDS
Bibliographic record
Abstract
HNF4α, also referred as maturity onset diabetes of the young (MODY-1), is a transcription factor that regulates differentiation, inflammation and metabolism. HNF4α regulatory function of carbohydrate-lipid metabolism has been mostly studied in relation to liver and pancreatic functions. Since the gut can actively participate in regulating metabolism, we have investigated HNF4α potential regulatory role in this context. To evaluate the effect of intestinal epithelial conditional deletion of HNF4α on lipid metabolism. Control and HNF4α mutant mice were fed with a high-fat diet (HFD) composed of 21.3% protein, 23.6% fat and 41.2% carbohydrate. Physiological parameters were measured using metabolic cages. Fatty acids (fecal, tissular and plasmatic) were assayed by gas chromatographic analysis. Circulating hormones were assessed by ELISA. The intestinal transcriptome was analyzed by qPCR and Affymetrix microarrays. HNF4α mutant mice maintained on HFD were resistant to weight gain as opposed to control mice. This observation was correlated with a significant reduction of visceral adiposity and hepatic lipid storage in mutant mice when compared to controls. Food consumption was not significantly altered among both groups. To investigate whether this phenotype was dependent on altered intestinal epithelial lipid absorption, we assessed lipid transport by measuring residual fecal as well as circulating fatty acids. HNF4α mutant mice exposed to HFD displayed similar levels of fatty acids both in the feces and in circulation when compared to controls. To explore how intestinal epithelial cells could interfere on the resistance to obesity phenotype, transcriptome profiles were compared between mutant and control mice. No specific expression change was observed among gene transcripts linked to lipid transport and metabolism. However, the gastric inhibitory peptide (GIP) gene transcript was found to be significantly reduced in mutant mice. ELISA confirmed a drastic 90% reduction of GIP circulating levels in mutant mice. Conditional deletion of HNF4α from the intestinal epithelium led to a resistance to HFD-induced obesity. This phenomenon was not dependent on gut lipid malabsorption. Since GIP expression is functionally linked to adipose tissue and control obesity state, investigation are currently undergoing to explore a relationship between intestinal epithelial HNF4α regulatory action on GIP hormone expression and obesity outcome. 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".