TY - JOUR
T1 - High fat diet induced obesity alters endocannabinoid and ghrelin mediated regulation of components of the endocannabinoid system in nodose ganglia
AU - Christie, Stewart
AU - O'Rielly, Rebecca
AU - Li, Hui
AU - Wittert, Gary A.
AU - Page, Amanda J.
PY - 2020/9
Y1 - 2020/9
N2 - Background: Ghrelin and anandamide (AEA) can regulate the sensitivity of gastric vagal afferents to stretch, an effect mediated via the transient receptor potential vanilloid 1 (TPRV1) channel. High fat diet (HFD)-induced obesity alters the modulatory effects of ghrelin and AEA on gastric vagal afferent sensitivity. This may be a result of altered gastric levels of these hormones and subsequent changes in the expression of their receptors. Therefore, the current study aimed to determine the effects of ghrelin and AEA on vagal afferent cell body mRNA content of cannabinoid 1 receptor (CB1), ghrelin receptor (GHSR), TRPV1, and the enzyme responsible for the breakdown of AEA, fatty acid amide hydrolase (FAAH). Methods: Mice were fed a standard laboratory diet (SLD) or HFD for 12wks. Nodose ganglia were removed and cultured for 14 h in the absence or presence of ghrelin or methAEA (mAEA; stable analogue of AEA). Relative mRNA content of CB1, GHSR, TRPV1, and FAAH were measured. Results: In nodose cells from SLD-mice, mAEA increased TRPV1 and FAAH mRNA content, and decreased CB1 and GHSR mRNA content. Ghrelin decreased TRPV1, CB1, and GHSR mRNA content. In nodose cells from HFD-mice, mAEA had no effect on TRPV1 mRNA content, and increased CB1, GHSR, and FAAH mRNA content. Ghrelin decreased TRPV1 mRNA content and increased CB1 and GHSR mRNA content. Conclusions: AEA and ghrelin modulate receptors and breakdown enzymes involved in the mAEA-vagal afferent satiety signalling pathways. This was disrupted in HFD-mice, which may contribute to the altered vagal afferent signalling in obesity.
AB - Background: Ghrelin and anandamide (AEA) can regulate the sensitivity of gastric vagal afferents to stretch, an effect mediated via the transient receptor potential vanilloid 1 (TPRV1) channel. High fat diet (HFD)-induced obesity alters the modulatory effects of ghrelin and AEA on gastric vagal afferent sensitivity. This may be a result of altered gastric levels of these hormones and subsequent changes in the expression of their receptors. Therefore, the current study aimed to determine the effects of ghrelin and AEA on vagal afferent cell body mRNA content of cannabinoid 1 receptor (CB1), ghrelin receptor (GHSR), TRPV1, and the enzyme responsible for the breakdown of AEA, fatty acid amide hydrolase (FAAH). Methods: Mice were fed a standard laboratory diet (SLD) or HFD for 12wks. Nodose ganglia were removed and cultured for 14 h in the absence or presence of ghrelin or methAEA (mAEA; stable analogue of AEA). Relative mRNA content of CB1, GHSR, TRPV1, and FAAH were measured. Results: In nodose cells from SLD-mice, mAEA increased TRPV1 and FAAH mRNA content, and decreased CB1 and GHSR mRNA content. Ghrelin decreased TRPV1, CB1, and GHSR mRNA content. In nodose cells from HFD-mice, mAEA had no effect on TRPV1 mRNA content, and increased CB1, GHSR, and FAAH mRNA content. Ghrelin decreased TRPV1 mRNA content and increased CB1 and GHSR mRNA content. Conclusions: AEA and ghrelin modulate receptors and breakdown enzymes involved in the mAEA-vagal afferent satiety signalling pathways. This was disrupted in HFD-mice, which may contribute to the altered vagal afferent signalling in obesity.
KW - CB1
KW - Endocannabinoids
KW - Ghrelin
KW - TRPV1
KW - Vagal afferents
UR - http://www.scopus.com/inward/record.url?scp=85087990346&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1159744
U2 - 10.1016/j.peptides.2020.170371
DO - 10.1016/j.peptides.2020.170371
M3 - Article
C2 - 32659299
AN - SCOPUS:85087990346
SN - 0196-9781
VL - 131
JO - Peptides
JF - Peptides
M1 - 170371
ER -