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

Yokota‐Nakagi, Naoko; Takahashi, Haruka; Kawakami, M; Takamata, Akira; Uchida, Yuzo; Morimoto, Keiko

doi:10.3390/nu12040907

Cited by 13 publications

(18 citation statements)

References 49 publications

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“…In this study, E2 replacement suppressed the increase in energy intake and body weight in HFD‐fed OVX rats more strongly than in NCD‐fed rats, as already shown in our previous report (Yokota‐Nakagi et al, 2020). Contrarily, a previous study reported that food intake was slightly lower in OVX mice than E2‐replaced mice fed on HFD, despite being more obese (Camporez et al, 2013).…”

Section: Discussionsupporting

confidence: 90%

“…Protein levels from the liver and muscles were analyzed by western blotting according to previously published protocols (Kawakami et al, 2018; Yokota‐Nakagi et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…The total weight of the mesenteric, kidney‐genital, and retroperitoneal adipose tissues was calculated to determine the weight of visceral adipose tissue. The weight of the inguinal adipose tissue was evaluated as representative of that of the subcutaneous adipose tissue in each rat (Yokota‐Nakagi et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

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Estradiol replacement improves high‐fat diet‐induced insulin resistance in ovariectomized rats

Yokota‐Nakagi

Omoto

Tazumi

et al. 2022

Physiological Reports

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The role of 17β‐estradiol (E2) in high‐fat diet (HFD)‐induced alteration of the protein kinase B (Akt) signaling pathway in ovariectomized (OVX) rats is unclear. Therefore, we examined whether chronic estrogen replacement restores HFD‐induced impairment in insulin sensitivity by its effects concomitant with alterations in the Akt isoform 2 (Akt2) and Akt substrate of 160 kDa (AS160) phosphorylation in muscles of OVX rats. Nine‐week‐old female Wistar rats underwent ovariectomy under anesthesia; after 4 weeks, subcutaneous implantation of either E2 or placebo (PL) pellets was performed, and HFD feeding was initiated. Intravenous glucose tolerance tests were performed to assess insulin sensitivity. Following insulin injection into rats’ portal vein, the liver and gastrocnemius muscle were dissected for insulin signaling analysis. We observed that HFD increased energy intake and body weight in the PL group; however, it was temporarily decreased in the E2 group. Adipose tissue accumulation was larger in HFD‐fed rats than in normal chow diet (NCD)‐fed rats in the PL group; however, this difference was not observed in the E2 group. HFD reduced insulin sensitivity in the PL group only. In vivo insulin stimulation increased Akt2 phosphorylation in the muscles of NCD‐fed rats in both groups. In contrast, HFD affected insulin‐stimulated phosphorylation of Akt2 and AS160 in the muscles of rats in the PL group but not in the E2 group. Our data suggest that E2 replacement improves HFD‐induced insulin resistance, and this effect is accompanied by the alterations in the Akt2 and AS160 phosphorylation in insulin‐stimulated muscles of OVX rats.

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Section: Discussionsupporting

confidence: 90%

“…Protein levels from the liver and muscles were analyzed by western blotting according to previously published protocols (Kawakami et al, 2018; Yokota‐Nakagi et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

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Estradiol replacement improves high‐fat diet‐induced insulin resistance in ovariectomized rats

Yokota‐Nakagi

Omoto

Tazumi

et al. 2022

Physiological Reports

Self Cite

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“…As E 2 treatment has previously been shown to reduce OVX-induced weight gain in both mice (Couse and Couse and Korach, 1999 ; Litwak et al, 2014 ) and rats ( Hertrampf et al, 2006 ; Sibonga et al, 1998 ; Wegorzewska et al, 2008 ), it was surprising that E 2 -treated mice did not exhibit significantly lower body weights than vehicle-treated mice. This lack of effect may be at least partially mediated by our use of a standard diet instead of a high-fat diet, as supported by previous rat ( Weigt et al, 2012 ; Yokota-Nakagi et al, 2020 ) and mouse studies ( Litwak et al, 2014 ). It is not surprising, however, to find that neither DPN nor EGX358 reduced weight gain compared to vehicle, as previous studies report mixed results, such that either no effect of phytoestrogen diets or ERβ agonist treatment was observed in rats ( Hertrampf et al, 2007 , 2008 ; Weigt et al, 2012 ), positive effects were found only under high-fat diet conditions in wild-type compared to ERβ knockout mice ( Foryst-Ludwig et al, 2008 ), or negative effects were shown under standard diet conditions in mice ( Said et al, 2018 ).…”

Section: Discussionmentioning

confidence: 62%

Long-term oral administration of a novel estrogen receptor beta agonist enhances memory and alleviates drug-induced vasodilation in young ovariectomized mice

Fleischer

Schalk

Wetzel

et al. 2021

Hormones and Behavior

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Development of estrogen therapies targeting the β (ERβ) but not α (ERα) estrogen receptor is critically needed for the treatment of negative menopausal symptoms, as ERα activation increases health risks like cancer. Here, we determined the effects of long-term oral treatment with EGX358, a novel highly selective ERβ agonist, on memory, vasodilation, and affect in young ovariectomized mice. Mice were orally gavaged daily for 9 weeks with vehicle, 17β-estradiol (E 2 ), the ERβ agonist diarylpropionitrile (DPN), or EGX358 at doses that enhance memory when delivered acutely. Tail skin temperature was recorded as a proxy for vasodilation following injection of vehicle or senktide, a tachykinin receptor 3 agonist used to model hot flashes. Anxiety-like behavior was assessed in the open field (OF) and elevated plus maze (EPM), and depression-like behavior was measured in the tail suspension (TST) and forced swim tests (FST). Finally, memory was assessed in object recognition (OR) and object placement (OP) tasks. E 2 , DPN, and EGX358 reduced senktide-mediated increases in tail skin temperature compared to vehicle. All three treatments also enhanced memory in the OR and OP tasks, whereas vehicle did not. Although E 2 increased time spent in the center of the OF, no other treatment effects were observed in the OF, EPM, TST, or FST. These data suggest that long-term ERβ activation can reduce hot flash-like symptoms and enhance spatial and object recognition memories in ovariectomized mice. Thus, the highly selective ERβ agonist EGX358 may be a promising avenue for reducing menopause-related hot flashes and memory dysfunction.

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“…As ovarian function declines, estrogen production and estrogen receptor function also decline, leading to abdominal fat accumulation and metabolic abnormalities in menopausal women [ 1 ]. Estrogen plays an important role in controlling food intake and body weight [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of the Gut Microbiota Structure with Probiotics and Isoflavone Alleviates Metabolic Disorder in Ovariectomized Mice

Chen

Wang

et al. 2021

Nutrients

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The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.

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

Cited by 13 publications

References 49 publications

Estradiol replacement improves high‐fat diet‐induced insulin resistance in ovariectomized rats

Estradiol replacement improves high‐fat diet‐induced insulin resistance in ovariectomized rats

Long-term oral administration of a novel estrogen receptor beta agonist enhances memory and alleviates drug-induced vasodilation in young ovariectomized mice

Modulation of the Gut Microbiota Structure with Probiotics and Isoflavone Alleviates Metabolic Disorder in Ovariectomized Mice

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