Ghrelin Blunts Adrenergic‐Stimulated Lipolysis in Subcutaneous and Visceral Adipose Tissue Ex Vivo, but not In Vivo
Authors: Cervone Daniel T , Dyck David J 
Published: June 2021

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 (Serine563/660) 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.