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

Naoko Yokota-Nakagi,Haruka Takahashi,Yuki Uchida,Mizuho Kawakami,Akira Takamata,Keiko Morimoto

doi:10.3390/nu12040907

Naoko Yokota-Nakagi, Haruka Takahashi + Show 4 more

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https://doi.org/10.3390/nu12040907

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Journal: Nutrients	Publication Date: Mar 26, 2020
Citations: 12	License type: CC BY 4.0

Affiliation: Kyoto Koka Women's University, Nara Women's University

Abstract

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.

Highlights

Obesity, defined as excessive fat accumulation, has become a worldwide epidemic [1]
Because intranuclear c-Fos is the product of the immediate-early-gene c-fos, an established marker of changes in neuronal activity in response to stimuli in rodents [26,27], these findings indicate that ghrelin activates orexigenic neurons in arcuate nucleus (ARC), resulting in an increase in food intake
The present study shows that E2 replacement reduces energy intake from high-fat diet (HFD) by suppressing orexigenic effects of ghrelin via downregulations of ghrelin and growth hormone secretagogue receptor (GHSR) proteins levels in the stomach orexigenic effects of ghrelin via downregulations of ghrelin and GHSR proteins levels in the stomach of HFD-fed OVX rats

Summary

Introduction

Obesity, defined as excessive fat accumulation, has become a worldwide epidemic [1]. Overweight and fat accumulation are associated with many adverse health outcomes, including type 2 diabetes, stroke, and heart disease [2]. Some studies have shown that dietary composition, high-fat diet (HFD), promotes obesity in humans [3] and mice [4]. The onset of menopause is accompanied by increases in energy intake and appetite and a decrease in energy consumption, followed by an increase in total body fat and visceral adipose tissue mass [7,8]. Hormone replacement therapy (HRT) attenuates body weight gain and fat accumulation in postmenopausal women [9,10]. Previous studies using ovariectomized (OVX) rats, an animal model widely used for studying the pathology of human menopause, showed that 17β-estradiol (E2) replacement suppresses body weight gain and fat accumulation and enhanced whole-body energy consumption not Nutrients 2020, 12, 907; doi:10.3390/nu12040907 www.mdpi.com/journal/nutrients

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