Abstract 290: Key Intestinal Genes Involved in Lipoprotein Metabolism Are Downregulated in Insulin-Resistant Males
Bibliographic record
Abstract
Recent studies indicate that insulin-resistance (IR) is associated with elevated levels of triglyceride-rich lipoproteins (TRL), including apoB-48-containing TRL of intestinal origin, in both the fasted and post-prandial states. This is of interest because elevated levels of intestine-derived lipoproteins are associated with increased cardiovascular disease risk. However, the mechanisms underlying the overaccumulation of apoB-48-containing TRL in IR have not been fully characterized in human. Therefore, the objective of this study was to examine the relationships between apoB-48-containing TRL kinetics and expression of key intestinal genes involved in lipid and lipoprotein metabolism in nondiabetic, IR males compared with insulin-sensitive (IS) males matched for age and waist circumference. A total of 30 nondiabetic caucasian males were chosen for extremes of insulin sensitivity (14 IR and 16 IS subjects) and matched for age and waist circumference. In vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D3]leucine for 12h in the fed state in all subjects. Expression of key intestinal genes involved in lipid and lipoprotein metabolism was compared by real-time PCR quantification in duodenal biopsy specimens from IR and IS participants taken in the fasted state. TRL apoB-48 pool size (PS) and production rate (PR) were increased by 105% (P<0.0001) and 45% (P=0.03), respectively in IR subjects compared with IS subjects. Expression of the nuclear transcription factors SREBP-2, SREBP1-C and HNF4α was significantly reduced by 31%, 28% and 25%, respectively in IR subjects. Similarly, many key genes involved in cholesterol, fatty acid, triglyceride and lipoprotein metabolism were significantly downregulated in IR individuals. In IR participants, intestinal expression of HMG CoAR, ACC1, SCD1, DGAT2, apoB and MTP was significantly reduced compared with IS subjects. Intestinal MTP expression was inversely correlated with TRL apoB-48 PS (r=-0.50, P=0.005) and PR (r=-0.32, P=0.07). These data suggest that IR is associated with intestinal overproduction of lipoproteins and downregulation of key intestinal genes involved in lipid/lipoprotein metabolism. Downregulation of these genes in the fasted state could represent an adaptive response to IR state.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".