Insulin Resistance Is Inversely Associated with the Intestinal Expression of Key Genes Involved in Chylomicron Assembly and Secretion
Bibliographic record
Abstract
Background Insulin resistance is a chronic metabolic disorder associated with an overproduction of atherogenic intestinal triglyceride‐rich lipoproteins (TRLs). However, the mechanisms underlying this increased secretion of intestinal TRLs remain to be fully understood. The objective of the present study was to evaluate the association between the homeostasis model assessment of insulin‐resistance (HOMA‐IR) index and the intestinal expression of key genes involved in chylomicron assembly and secretion in a large sample of non‐diabetic men. Methods Duodenal biopsies were obtained by gastroduodenoscopy in 105 non‐diabetic men. Gene expression was measured using quantitative PCR in duodenal biopsy samples. Anthropometric parameters and fasting plasma glucose and insulin concentrations were measured in all participants. Results Participants' mean age (±SD) was 37.7 ± 11.1 years (range: 21.0 to 65.0 years). Mean BMI was 31.8 ± 4.3 kg/m 2 (range: 20.4 to 43.8 kg/m 2 ) and mean HOMA‐IR index was 4.10 ± 1.64 (range: 1.02 to 10.02). The HOMA‐IR index was inversely associated with the duodenal expression of microsomal triglyceride transfer protein (MTP) (r=‐0.23; P =0.02), acetyl‐coenzyme A synthetase 1 (ACS1) (r=−0.22; P =0.03), diacylglycerol O‐acyltransferase 1 (DGAT1) (r=−0.25; P =0.01) and DGAT2 (r=−0.24; P =0.02). These associations were independent of body mass index (BMI), waist circumference and age. There was no significant association between the HOMA‐IR index and the duodenal expression of apolipoprotein (apo) B (r=−0.15; P =0.15) and SAR1 gene homolog B (SAR1B) (r=−0.20; P =0.07). Duodenal expression of MTP was positively associated with the expression of apo B (r=0.60; P <0.0001), ACS1 (r=0.57; P <0.0001), DGAT1 (r=0.72; P <0.0001), DGAT2 (r=0.77; P <0.0001) and SAR1B (SAR1B) (r=0.66; P <0.0001). Using multiple linear regression models, the HOMA‐IR index was the only factor significantly associated with variations in the duodenal expression of MTP, DGAT1 and DGAT2, whereas BMI and the HOMA‐IR index both contributed significantly to the variance of ACS1 expression. Conclusions This study demonstrates that insulin‐resistance is inversely associated with expression of the key genes involved in chylomicron assembly in the duodenum, independent of variations in BMI, waist circumference and age. The downregulation of the expression of these genes may represent an adaptive response to the chronic insulin‐resistance to decrease chylomicron secretion.
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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 | 0.001 |
| 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) | 0.002 | 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".