Short-Term Unacylated Ghrelin Administration Improves Pyruvate Tolerance Without Chronically Altering Skeletal Muscle, Liver, or Adipose Tissue Insulin Response in Healthy Rats.
- 1Department of Human Health Sciences, University of Guelph, Guelph, Ontario, Canada.
Abstract
Unacylated ghrelin (unAG) is a metabolically active hormone, acutely stimulating fatty acid oxidation in skeletal muscle while promoting lipogenesis and inhibiting lipolysis in adipose tissue. Given these acute effects, we hypothesized that repeated unAG administration would improve skeletal muscle insulin response and that this would be associated with reduced muscle lipid storage. We treated healthy male Sprague-Dawley rats with twice-daily subcutaneous unAG (200 μg; 400 μg total daily) for 5 days. UnAG treatment did not alter glucose uptake or AKT activation basally, or in response to low or high insulin concentrations when assessed ex vivo in oxidative or glycolytic skeletal muscle, or when muscle was pre-exposed to a high-palmitate stress. Protein content of mitochondrial markers (CPT1B, citrate synthase, COXIV) also remained unchanged with treatment in both muscle types. Interestingly, UnAG-treated animals had a reduced glycemic response to pyruvate administration; however, content of hepatic glucose production-associated proteins and liver AKT response to insulin remained unchanged. UnAG treatment tended to increase LPL protein content in visceral adipose tissue (p = 0.07), but did not alter AKT or HSL phosphorylation in response to an insulin bolus in either subcutaneous or visceral adipose tissue. Finally, triacylglycerol content in the red and white gastrocnemius muscle, as well as in the liver, was unchanged by unAG administration. Overall, these findings indicate that short-term unAG treatment improves pyruvate tolerance, but that it does not exert persistent metabolic changes to skeletal muscle, liver, or adipose tissue substrate metabolism in healthy rats.
Related
- Vitamin B1 administration attenuates anxiety and depression-like behaviors induced by nicotine abstinence in chronically stressed rats
- Intratracheal Administration of Benzbromarone Attenuates Pulmonary Vascular Remodeling and Improves Survival in Rats with Monocrotaline-Induced Pulmonary Hypertension
- Peri-Ovarian Mitochondrial Administration Improves Surrogate Markers of Ovarian Function in Aged Rats: Free Versus Alginate-Encapsulated Mesenchymal Stromal Cell-Derived Mitochondria
- Antibody co-administration robustly improves proton therapy with radiosensitizing nanoparticles: a mathematical modeling study
- Injury improves tolerance to acute heat stress through induction of heat shock protein expression in the annelid Pristina leidyi
BibTeX
@article{notaro2026shortterm,
title = {{Short-Term Unacylated Ghrelin Administration Improves Pyruvate Tolerance Without Chronically Altering Skeletal Muscle, Liver, or Adipose Tissue Insulin Response in Healthy Rats.}},
author = {Nicole M Notaro and Sofia F Prizio and Brielle R Caruso and David J Dyck},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2026},
month = nov,
doi = {10.1096/fj.202604205r},
url = {https://europepmc.org/article/MED/42969040},
note = {CC BY},
}
RIS
TY - JOUR
TI - Short-Term Unacylated Ghrelin Administration Improves Pyruvate Tolerance Without Chronically Altering Skeletal Muscle, Liver, or Adipose Tissue Insulin Response in Healthy Rats.
AU - Nicole M Notaro
AU - Sofia F Prizio
AU - Brielle R Caruso
AU - David J Dyck
PY - 2026
DA - 2026/11/01
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DO - 10.1096/fj.202604205r
UR - https://europepmc.org/article/MED/42969040
AB - Unacylated ghrelin (unAG) is a metabolically active hormone, acutely stimulating fatty acid oxidation in skeletal muscle while promoting lipogenesis and inhibiting lipolysis in adipose tissue. Given these acute effects, we hypothesized that repeated unAG administration would improve skeletal muscle insulin response and that this would be associated with reduced muscle lipid storage. We treated healthy male Sprague-Dawley rats with twice-daily subcutaneous unAG (200 μg; 400 μg total daily) for 5 days. UnAG treatment did not alter glucose uptake or AKT activation basally, or in response to low or high insulin concentrations when assessed ex vivo in oxidative or glycolytic skeletal muscle, or when muscle was pre-exposed to a high-palmitate stress. Protein content of mitochondrial markers (CPT1B, citrate synthase, COXIV) also remained unchanged with treatment in both muscle types. Interestingly, UnAG-treated animals had a reduced glycemic response to pyruvate administration; however, content of hepatic glucose production-associated proteins and liver AKT response to insulin remained unchanged. UnAG treatment tended to increase LPL protein content in visceral adipose tissue (p = 0.07), but did not alter AKT or HSL phosphorylation in response to an insulin bolus in either subcutaneous or visceral adipose tissue. Finally, triacylglycerol content in the red and white gastrocnemius muscle, as well as in the liver, was unchanged by unAG administration. Overall, these findings indicate that short-term unAG treatment improves pyruvate tolerance, but that it does not exert persistent metabolic changes to skeletal muscle, liver, or adipose tissue substrate metabolism in healthy rats.
SN - 0892-6638
SN - 1530-6860
ER -