Ghrelin Directly Stimulates Fatty Acid Oxidation in Skeletal Muscle
Bibliographic record
Abstract
Ghrelin is classically known as a central appetite stimulating hormone, but has recently been recognized to have a significant role in peripheral tissue energy metabolism. Given that ghrelin rapidly increases prior to entrained mealtimes, it is possible that ghrelin may act as part of a preparatory response to facilitate the metabolism of ingested glucose and lipids. Skeletal muscle is a major site for glucose and lipid disposal; however, the direct effects of ghrelin on this tissue remain understudied. Furthermore, studies examining the metabolic effects of in vivo ghrelin injections fail to distinguish independent effects of ghrelin from secondary effects such as increases in growth hormone. Therefore, the purpose of this study was to determine the direct effects of the two main isoforms of ghrelin, acylated (AG) and unacylated (UnAG) on fatty acid (FA) metabolism in isolated rat skeletal muscle. Specifically, we examined the effect of ghrelin (AG, UnAG) on labeled palmitate oxidation and incorporation into major lipid pools (diacylglycerol, DAG; triacylglycerol, TAG) under conditions of low glucose (5 mM) or high glucose concentrations (10 mM) . Soleus (SOL) and extensor digitorum longus (EDL) were used as representative oxidative and glycolytic muscles and 1mM palmitate was used in the medium throughout. We hypothesized that ghrelin would facilitate the uptake of fatty acids into skeletal muscle thereby increasing oxidation and incorporation into lipid pools. SOL and EDL muscle strips were excised from male Sprague‐Dawley rats (~250 g) and incubated with either 150 ng/ml of AG or UnAG, or 2 mM of 5‐Aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), a known stimulant of fatty acid oxidation (positive control). To assess oxidation, sulfuric acid was added directly to the medium containing the muscle to release 14 CO 2 , which was trapped in a suspended vial containing benzethonium hydroxide. In a separate set of experiments, 14 C palmitate incorporation into muscle lipid pools was assessed by extracting lipids into a 2:1 chloroform:methanol solution and spotting on a thin layer chromatography plate. A repeated measures one‐way ANOVA uncorrected for Fisher's LSD was performed and significance was accepted at p≤0.05. In agreement with our hypothesis, both isoforms of ghrelin (AG and UnAG) stimulated palmitate oxidation. At 10 mM glucose, both AG and UnAG increased palmitate oxidation (~40%; p<0.05) in SOL and EDL. At the lower glucose concentration (5 mM), UnAG increased palmitate oxidation (SOL, 41%; EDL, 27%; p<0.05); and a near significant trend of AG induced FA oxidation was observed in EDL (23%; p=0.07), but not in SOL (14%, p=0.258). Deposition of labeled fatty acids into DAG and TAG pools was unaffected by AG and UnAG, suggesting that the acute effect of ghrelin on muscle is solely directed at oxidation. In summary, ghrelin has a direct, acute stimulatory effect on fatty acid metabolism in both oxidative and glycolytic skeletal muscle. This effect appears to be directed only at oxidation, and occurs regardless of the glucose environment. Further experiments will be performed to assess the effect of ghrelin on fat breakdown (lipolysis) in muscle and the underlying cellular signaling mechanisms involved. Support or Funding Information 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 | 0.001 |
| 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 | 0.001 |
| 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".