Estradiol Replacement Improves High-Fat Diet-Induced Obesity by Suppressing the Action of Ghrelin in Ovariectomized Rats.

Yokota-Nakagi N, Takahashi H, Kawakami M, Takamata A, Uchida Y, Morimoto K

Nutrients26 Mar 2020Cited by 19 (Europe PMC)

PMID32224927PMCIDPMC7230822DOI10.3390/nu12040907PepBankPUB-32224927

Summary

This study aims to investigate the effects of estradiol replacement on the orexigenic action of ghrelin in ovariectomized (OVX) obese rats fed with a high-fat diet (HFD). Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding. After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups. The ghrelin protein and mRNA levels, as well as GHSR protein in stomach, were analyzed by Western blotting and real-time PCR. HFD increased energy intake and body weight in the Pla group, while it temporarily reduced these in the E2 group. GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group. Furthermore, gastric ghrelin and GHSR protein levels were lower in the E2 group than in the Pla group, but plasma acyl ghrelin levels were similar in both groups. Our results suggest that E2 replacement improves obesity by inhibiting the orexigenic action of ghrelin via downregulation of ghrelin and its receptor in stomach in HFD-fed OVX rats.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking GHRP-6.

01AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In ovariectomized rats with placebo pellets, the GHRP‑6 challenge increased high-fat diet intake.
In plain wordsIn rats with ovaries removed, a GHRP‑6 challenge increased high-fat food intake in the placebo-pellet group.
Peptide
GHRP-6
Outcome
IncreaseHigh-fat diet intake with placebo pellets
Study
ratn: not reported in source
Ovariectomized Wistar rats fed a high-fat diet
Outcome group
Appetite and food intake · Metabolic and weight
Source sentences
Summary
GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group.
2 context sentences(design, population, supporting numbers)
Summary · context
Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding.
Summary · context
After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3222492701
02AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In ovariectomized rats with estradiol pellets, the GHRP‑6 challenge did not enhance high-fat diet intake.
In plain wordsIn rats with ovaries removed, a GHRP‑6 challenge did not increase high-fat food intake in the estradiol group.
Peptide
GHRP-6
Outcome
No significant changeHigh-fat diet intake with estradiol pellets
Study
ratn: not reported in source
Ovariectomized Wistar rats fed a high-fat diet
Outcome group
Appetite and food intake · Metabolic and weight
Source sentences
Summary
GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group.
2 context sentences(design, population, supporting numbers)
Summary · context
Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding.
Summary · context
After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3222492702
03AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In ovariectomized rats with placebo pellets, the GHRP‑6 challenge activated hypothalamic arcuate neurons.
In plain wordsIn rats with ovaries removed, a GHRP‑6 challenge activated arcuate brain neurons in the placebo-pellet group.
Peptide
GHRP-6
Outcome
IncreaseArcuate neuron activation with placebo pellets
Study
ratn: not reported in source
Ovariectomized Wistar rats fed a high-fat diet
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group.
2 context sentences(design, population, supporting numbers)
Summary · context
Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding.
Summary · context
After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3222492703
04AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In ovariectomized rats with estradiol pellets, the GHRP‑6 challenge did not activate hypothalamic arcuate neurons.
In plain wordsIn rats with ovaries removed, a GHRP‑6 challenge did not activate arcuate brain neurons in the estradiol group.
Peptide
GHRP-6
Outcome
No significant changeArcuate neuron activation with estradiol pellets
Study
ratn: not reported in source
Ovariectomized Wistar rats fed a high-fat diet
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group.
2 context sentences(design, population, supporting numbers)
Summary · context
Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding.
Summary · context
After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3222492704

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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