Estradiol protects against ovariectomy-induced susceptibility to the anabolic effects of glucocorticoids in rats

Souza, Camila F. de; Stopa, Larissa Rugila S.; Santos, Geisielle Fernandes; Takasumi, Leticia Correa N.; Martins, Andressa Busetti; Garnica-Siqueira, Marcela Cristina; Ferreira, Renan Nascimento; Andrade, Fábio Goulart de; Leite, Cristiane Mota; Zaia, Dimas Augusto Morozin; Zaia, Cássia Thaïs Bussamra Vieira; Uchôa, Ernane Torres

doi:10.1016/j.lfs.2018.12.037

Cited by 19 publications

(17 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding that corticosterone-treated female mice tended to have larger WAT depots but smaller adipocytes, together with a lower mRNA expression of Adamts1 and Lep , than do corticosterone-treated male mice suggests that female mice displayed more hyperplastic expansion in WATs than did male mice upon corticosterone treatment. This is in accordance with a previous study showing that corticosterone-induced adipocyte expansion was greater in ovariectomized female rats than in sham-operated female rats, which suggests a role for sex steroids in the sex difference in adipose depot expandability (52).…”

Section: Discussionsupporting

confidence: 93%

“…For instance, estrogen depletion in female mice resulted in a GC-driven development of hepatic steatosis (45). The consequences of this on whole-body metabolism was not addressed in the aforementioned study, but another study revealed that corticosterone-induced metabolic derangements, such as BW gain and WAT expansion, were more severe in ovariectomized than in sham-operated female rats and were counteracted by estradiol supplementation (52). Recently, androgens were also reported to modulate GR activity in liver and adipose tissue of male mice (62).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex Difference in Corticosterone-Induced Insulin Resistance in Mice

et al. 2019

View full text Add to dashboard Cite

Prolonged exposure to glucocorticoids (GCs) causes various metabolic derangements. These include obesity and insulin resistance, as inhibiting glucose utilization in adipose tissues is a major function of GCs. Although adipose tissue distribution and glucose homeostasis are sex-dependently regulated, it has not been evaluated whether GCs affect glucose metabolism and adipose tissue functions in a sex-dependent manner. In this study, high-dose corticosterone (rodent GC) treatment in C57BL/6J mice resulted in nonfasting hyperglycemia in male mice only, whereas both sexes displayed hyperinsulinemia with normal fasting glucose levels, indicative of insulin resistance. Metabolic testing using stable isotope-labeled glucose techniques revealed a sex-specific corticosterone-driven glucose intolerance. Corticosterone treatment increased adipose tissue mass in both sexes, which was reflected by elevated serum leptin levels. However, female mice showed more metabolically protective adaptations of adipose tissues than did male mice, demonstrated by higher serum total and high-molecular-weight adiponectin levels, more hyperplastic morphological changes, and a stronger increase in mRNA expression of adipogenic differentiation markers. Subsequently, in vitro studies in 3T3-L1 (white) and T37i (brown) adipocytes suggest that the increased leptin and adiponectin levels were mainly driven by the elevated insulin levels. In summary, this study demonstrates that GC-induced insulin resistance is more severe in male mice than in female mice, which can be partially explained by a sex-dependent adaptation of adipose tissues.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Sex Difference in Corticosterone-Induced Insulin Resistance in Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In addition to having higher body mass, the OVX group had higher retroperitoneal adipose tissue mass (i.e., a visceral depot) and lower liver mass compared with the sham group, in agreement with previous studies [4,63]. The increase in body fat also concurs with findings from human studies done by our group [1] and others [53,64], demonstrating an accelerated increase in adiposity during menopause.…”

Section: Discussionsupporting

confidence: 92%

“…Based on the current evidence it remains unclear whether OVX-induced weight gain is due to reduced energy expenditure or increased energy intake. Some previous studies have observed an increase in energy intake following OVX in rats [3,4,48]. However, in these studies there was only a short-term follow-up (∼1-month post-surgery) on energy intake.…”

Section: Discussionmentioning

confidence: 98%

Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise

Lee,

Nissinen,

Yla-Outinen

et al. 2024

Preprint

View full text Add to dashboard Cite

Objective: Estrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon. Methods: We studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n=64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography. Results: OVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p≤0.005). OVX reduced maximal running capacity by 17% (p=0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p=0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p≤0.024). Conclusions: Our results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.

show abstract

“…Extensive studies have been conducted on the role of estrogen in various metabolisms, immunity, and inflammatory processes in rodents and humans [78]. Thanks to more sensitive and accurate proteomic techniques, a number of proteins and pathways in visceral fat were found in OVX rodent models [79]. Interestingly, Boldarine et al reported that OVX induced the upregulation of genes related to lipogenesis and downregulation of genes related to fatty acid oxidation [10].…”

Section: Alterations In Fatty Acid Metabolismmentioning

confidence: 99%

Energy Metabolism Changes and Dysregulated Lipid Metabolism in Postmenopausal Women

Jung

2021

Nutrients

120

View full text Add to dashboard Cite

Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make postmenopausal women vulnerable to body composition changes, muscle loss, and abdominal obesity; with a sedentary lifestyle, these changes affect overall energy expenditure and basal metabolic rate. In addition, fat redistribution due to hormonal changes leads to changes in body shape. In particular, increased bone marrow-derived adipocytes due to estrogen loss contribute to increased visceral fat in postmenopausal women. Enhanced visceral fat lipolysis by adipose tissue lipoprotein lipase triggers the production of excessive free fatty acids, causing insulin resistance and metabolic diseases. Because genes involved in β-oxidation are downregulated by estradiol loss, excess free fatty acids produced by lipolysis of visceral fat cannot be used appropriately as an energy source through β-oxidation. Moreover, aged women show increased adipogenesis due to upregulated expression of genes related to fat accumulation. As a result, the catabolism of ATP production associated with β-oxidation decreases, and metabolism associated with lipid synthesis increases. This review describes the changes in energy metabolism and lipid metabolic abnormalities that are the background of weight gain in postmenopausal women.

show abstract

Estradiol protects against ovariectomy-induced susceptibility to the anabolic effects of glucocorticoids in rats

Cited by 19 publications

References 62 publications

Sex Difference in Corticosterone-Induced Insulin Resistance in Mice

Sex Difference in Corticosterone-Induced Insulin Resistance in Mice

Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise

Energy Metabolism Changes and Dysregulated Lipid Metabolism in Postmenopausal Women

Contact Info

Product

Resources

About