Ghrelin and the Regulation of Peripheral Tissue Metabolism
Bibliographic record
Abstract
Introduction Ghrelin is a potent, appetite‐ and growth hormone (GH) ‐stimulating gastric hormone that has been recently shown to have important metabolic effects on insulin‐responsive peripheral tissues (eg. adipose tissue, skeletal muscle). Ghrelin increases exponentially prior to a meal, and rapidly declines to baseline after meal consumption. Therefore, it is important to elucidate any potential role that ghrelin may have in mediating carbohydrate and lipid metabolism surrounding entrained meal time. There is evidence, albeit limited, to suggest that both acylated (AG) and deacylated (DAG) ghrelin may act to potentiate glucose uptake in myocytes and inhibit the adrenergic stimulation of lipolysis in isolated adipocytes. Conversely, upon in vivo administration of ghrelin in humans, there is a marked decrease in insulin sensitivity and increases in local (adipose and skeletal muscle) indicators of lipolysis (glycerol). However, in vivo findings are confounded by factors such as the secondary increase in growth hormone, which can in itself stimulate lipolysis and influence glucose uptake. Methods Soleus (oxidative) and extensor digitorum longus (EDL, glycolytic) muscles, and subcutaneous (inguinal ‐ iWAT) and visceral (retroperitoneal ‐ RP) adipose tissue depots were isolated from male Sprague Dawley rats. Muscles were incubated in the presence of labelled 3‐methyl‐O‐glucose to assess the effect of AG and DAG (5 to 150 nM) on basal and insulin stimulated glucose uptake. Adipose tissue organ culture was used to assess glycerol release (index of lipolysis) following incubation with either vehicle, the beta‐3 agonist CL 316 243 (10uM), CL + AG (50nM), CL + DAG (50nM) or AG and DAG independently. Results AG and DAG had a no direct influence on basal (Con: 62 ± 9; AG: 56 ± 5; DAG: 78 ± 13 nmol/g/5min) or insulin‐stimulated (Con: 41 ± 3; Ins: 82 ± 5; Ins+AG: 65 ± 11; Ins+DAG: 94 ± 9 nmol/g/5min) glucose uptake in soleus (shown) or EDL skeletal muscle. The activation of insulin signaling protein pAkt (Ser 473 ) was also unchanged by ghrelin treatment. Compared to vehicle (iWAT: 0.54 ± 0.05; RP: 0.56 ± 0.08 mM/g) CL markedly increased rates of glycerol release in both iWAT (1.20 ± 0.06) and RP (1.91 ± 0.30) depots (p<0.05). This effect was abolished in the presence of both AG (iWAT: 0.79 ± 0.09; RP: 1.52 ± 0.12) and DAG (iWAT: 0.82 ± 0.05; RP: 1.44 ± 0.19) (p>0.05). AG (iWAT: 0.48 ± 0.08; RP: 0.54 ± 0.08) and DAG (iWAT: 0.62 ± 0.14; RP: 0.54 ± 0.09) did not independently affect glycerol release. These effects were observed following both 2h (shown) and 4h of treatment. Conclusions Ghrelin isoforms have no direct effect on skeletal muscle glucose uptake, but do inhibit adrenergic‐stimulated lipolysis in both subcutaneous and visceral adipose depots. Further work will consider whether ghrelin can act as a regulator of lipolysis in conjunction with other known pre and postprandial hormones (eg. GH, insulin). Finally, ghrelin action on cellular signaling underlying functional changes in lipolysis will be assessed (eg. HSL, ATGL, perilipin). These experiments will contribute to the accurate interpretation of AG and DAG's direct effects in peripheral tissue glucose and lipid metabolism. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC).
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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 | 0.001 |
| 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".