Ghrelin Blunts Adrenergic‐Stimulated Lipolysis in Subcutaneous and Visceral Adipose Tissue Ex Vivo, but not In Vivo
Bibliographic record
Abstract
Introduction Ghrelin is an appetite and growth hormone (GH) ‐stimulating gastric hormone. Ghrelin rises preprandially and immediately declines to baseline after meal consumption. Therefore, it is important to elucidate any potential role that ghrelin may have in mediating substrate metabolism surrounding entrained meal time. There is evidence to suggest that ghrelin may inhibit the adrenergic stimulation of lipolysis in isolated adipocytes, which would seem intuitive if we consider ghrelin as a meal‐priming signal, as there is unlikely to be a requirement to spare blood glucose following a meal. However, upon administration of ghrelin in humans, there are marked increases in local adipose and skeletal muscle rates of glycerol appearance, indicative of increased lipolysis. In vivo findings, though, are confounded by a secondary increase in GH, which may be lipolytic. Previously, using an ex vivo (adipose tissue organ culture) model, we have shown that both acylated (AG) and unacylated (UnAG) ghrelin blunt adrenergic (CL 316 243) stimulated lipolysis, with a corresponding reduction in the activation of hormone‐sensitive lipase (HSL). Our current experimental model is aimed at elucidating whether or not this newly found, direct role for ghrelin in mediating adipose tissue lipolysis can be replicated in vivo. Methods To date, subcutaneous iWAT and visceral RP adipose tissue depots have been harvested from healthy, male Sprague‐Dawley rats for the assessment of glycerol release following injection with either saline, CL (1mg/kg), CL + AG and CL + UnAG (50μg/kg). In vivo tissue and blood collection was done 30min following IP injection. Western blots were used to quantify the activation of markers associated with lipolysis. qPCR will be undertaken to assess markers of fatty acid storage (eg. fatty acid synthase). ELISA will be used to quantify GH, insulin and glucagon as potential circulating confounders. Results Ex vivo, AG and UnAG blunted CL‐stimulated lipolysis, but did not independently affect glycerol release or lipolytic signalling proteins (p>0.05) and were not pursued further with in vivo injection studies. When compared to saline (0.36 ± 0.06 mM), CL injection markedly increased the rates of glycerol release (0.77 ± 0.07 mM; p<0.05). There was no effect of co‐administration of CL with ghrelin isoforms on the CL‐mediated increase in glycerol release (AG: 0.77 ± 0.04; UnAG: 0.79 ± 0.04 mM). These outcomes were mirrored by signalling proteins, in that HSL (Serine 563/660 ) activation was significantly elevated with CL (iWAT: 2.80 ± 0.43; RP: 4.69 ± 1.23) compared to saline injection (iWAT: 0.78 ± 0.23; RP: 2.13 ± 1.03) and unchanged with the co‐injection ghrelin (iWAT ‐ CL+AG: 2.61 ± 0.54, CL+UnAG: 2.39 ± 0.22; RP – CL+AG: 6.83 ± 1.89, CL+UnAG: 11.66 ± 2.93). Conclusions We extend on previous findings and show that ghrelin directly inhibits adrenergic‐stimulated lipolysis in subcutaneous and visceral adipose depots. However, in the living animal, these actions appear to be confounded by other factors. Transcriptional markers of lipid storage will be used to elucidate whether ghrelin is also acting directly as a storage signal, beyond its inhibition of fatty acid mobilization. These experiments will be seminal in contributing to the interpretation of AG and UnAG's effects in adipose tissue lipid metabolism. Support or Funding Information Funded by NSERC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".