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Effects of Sex Hormones in the Regulation of Energy Metabolism...
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Effects of Sex Hormones in the Regulation of Energy Metabolism in Health and Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (14 October 2022) | Viewed by 19379

Special Issue Editor

Prof. Haifei Shi

E-Mail Website
Guest Editor
Department of Biology, Miami University, Oxford, OH, USA
Interests: energy metabolism; metabolic diseases; neuroendocrine; feeding; energy expenditure; adipose tissue; sex difference; stress; brain–gut–microbiome axis

Special Issue Information

Dear Colleagues,

Sex hormones play critical roles in the regulation of energy metabolism and related physiology and behavior, via triggering a variety of cellular and molecular mechanisms in various tissues and organs throughout the body, contributing to significant sex differences seen in health and disease conditions. Indeed, preclinical and clinical studies have reported sex differences in the development, progression, and treatment of metabolic diseases, including obesity, diabetes, cardiovascular diseases, eating disorders, gastrointestinal diseases, reproductive disorders, some types of cancers, and psychological and psychiatric disorders. Increasing research attention and efforts have been paid to sex differences in various metabolic systems and to potential influence of sex hormones in the aforementioned metabolic diseases. Levels and actions of sex hormones dynamically change at different life stages, such as puberty, pregnancy and lactation, and aging and menopause, which not only affect the inherent structures and cellular components but also cause distinct physiology and function of multiple organ systems throughout the lifespan. Recent research efforts and cutting-edge state-of-art technologies have greatly advanced our understanding of the roles of sex hormones in physiological functions and behavioral regulation, underlying cellular and molecular processes, as well as pathological development and progression of metabolic diseases. Many knowledge gaps and paradoxes still remain, however. In order to effectively develop novel therapeutic strategies that benefit patients of both sexes, a better understanding of mechanisms underlying the sex differences in behavior and metabolism and the influence of sex steroids is required. 

This Special Issue of Cells invites investigators to contribute original research articles and reviews from basic and translational preclinical studies that stimulate the continuing efforts to explore and understand the physiological and pathological roles of sex hormones in genetic, behavioral, physiological, cellular, and molecular mechanisms underlying sex-based differences in energy metabolism under both health and disease conditions. Research fields include but are not limited to (1) the impact of sex hormones on structure, molecular and cellular components, physiology, and function of various tissues and organs; (2) novel pathways employed by sex hormones and their receptors in multiple organ systems that regulate physiological functions and behaviors; (3) impact of sex hormonal changes at different life stages on different metabolic systems and behaviors; (4) interaction between sex hormones and central and peripheral nervous system involving their receptors and intracellular signaling pathways in the regulation of various metabolic systems, behaviors, and related disease development and potential treatment strategies; and (5) the latest technologies for evaluating and measuring sex hormone actions in basic and translational preclinical research.

Prof. Haifei Shi
Guest Editor

Manuscript Submission Information

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Keywords

  • Energy metabolism
  • Metabolic disorders
  • Central nervous system
  • Immune system
  • Adipose tissue
  • Liver
  • Brain–gut–microbiome axis
  • Gonadal hormones
  • Sex differences
  • Energy intake
  • Energy expenditure
  • Feeding behavior

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Published Papers (4 papers)

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Research

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26 pages, 3256 KiB  
Article
A Multi-Omics Study Revealing the Metabolic Effects of Estrogen in Liver Cancer Cells HepG2
by Minqian Shen, Mengyang Xu, Fanyi Zhong, McKenzie C. Crist, Anjali B. Prior, Kundi Yang, Danielle M. Allaire, Fouad Choueiry, Jiangjiang Zhu and Haifei Shi
Cells 2021, 10(2), 455; https://doi.org/10.3390/cells10020455 - 20 Feb 2021
Cited by 17 | Viewed by 5163
Abstract
Hepatocellular carcinoma (HCC) that is triggered by metabolic defects is one of the most malignant liver cancers. A much higher incidence of HCC among men than women suggests the protective roles of estrogen in HCC development and progression. To begin to understand the [...] Read more.
Hepatocellular carcinoma (HCC) that is triggered by metabolic defects is one of the most malignant liver cancers. A much higher incidence of HCC among men than women suggests the protective roles of estrogen in HCC development and progression. To begin to understand the mechanisms involving estrogenic metabolic effects, we compared cell number, viability, cytotoxicity, and apoptosis among HCC-derived HepG2 cells that were treated with different concentrations of 2-deoxy-d-glucose (2-DG) that blocks glucose metabolism, oxamate that inhibits lactate dehydrogenase and glycolysis, or oligomycin that blocks ATP synthesis and mitochondrial oxidative phosphorylation. We confirmed that HepG2 cells primarily utilized glycolysis followed by lactate fermentation, instead of mitochondrial oxidative phosphorylation, for cell growth. We hypothesized that estrogen altered energy metabolism via its receptors to carry out its anticancer effects in HepG2 cells. We treated cells with 17β-estradiol (E2), 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) an estrogen receptor (ER) α (ERα) agonist, or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), an ERβ agonist. We then used transcriptomic and metabolomic analyses and identified differentially expressed genes and unique metabolite fingerprints that are produced by each treatment. We further performed integrated multi-omics analysis, and identified key genes and metabolites in the gene–metabolite interaction contributed by E2 and ER agonists. This integrated transcriptomic and metabolomic study suggested that estrogen acts on estrogen receptors to suppress liver cancer cell growth via altering metabolism. This is the first exploratory study that comprehensively investigated estrogen and its receptors, and their roles in regulating gene expression, metabolites, metabolic pathways, and gene–metabolite interaction in HCC cells using bioinformatic tools. Overall, this study provides potential therapeutic targets for future HCC treatment. Full article
(This article belongs to the Special Issue Effects of Sex Hormones in the Regulation of Energy Metabolism in Health and Diseases)
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Review

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14 pages, 638 KiB  
Review
Sex-Dependent Differences in Colorectal Cancer: With a Focus on Obesity
by Prachi Wele, Xian Wu and Haifei Shi
Cells 2022, 11(22), 3688; https://doi.org/10.3390/cells11223688 - 20 Nov 2022
Cited by 15 | Viewed by 3371
Abstract
Colorectal cancer (CRC) is the third most common cancer and has the second highest cancer-related mortality in the world. The incident rates of CRC vary country-wise; however, population studies and data from different countries show a general increase in the CRC rate in [...] Read more.
Colorectal cancer (CRC) is the third most common cancer and has the second highest cancer-related mortality in the world. The incident rates of CRC vary country-wise; however, population studies and data from different countries show a general increase in the CRC rate in young adults, males, and females ≥65 years. CRC incidence is affected by age, sex, environmental, dietary, hormonal, and lifestyle factors. Obesity is a known disease that is spreading rapidly throughout the world. A large body of literature indicates that, among many conditions, obesity is the increasing cause of CRC. Even though obesity is one of the known factors for CRC development, limited studies are available that explain the mechanistic link between obesity, sex hormones, and CRC development. Thus, this review summarizes the literature and aims to understand sex-dependent differences in CRC, especially in the context of obesity. Full article
(This article belongs to the Special Issue Effects of Sex Hormones in the Regulation of Energy Metabolism in Health and Diseases)
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18 pages, 1254 KiB  
Review
Estrogenic Action in Stress-Induced Neuroendocrine Regulation of Energy Homeostasis
by Kristen N. Krolick and Haifei Shi
Cells 2022, 11(5), 879; https://doi.org/10.3390/cells11050879 - 3 Mar 2022
Cited by 7 | Viewed by 5733
Abstract
Estrogens are among important contributing factors to many sex differences in neuroendocrine regulation of energy homeostasis induced by stress. Research in this field is warranted since chronic stress-related psychiatric and metabolic disturbances continue to be top health concerns, and sex differences are witnessed [...] Read more.
Estrogens are among important contributing factors to many sex differences in neuroendocrine regulation of energy homeostasis induced by stress. Research in this field is warranted since chronic stress-related psychiatric and metabolic disturbances continue to be top health concerns, and sex differences are witnessed in these aspects. For example, chronic stress disrupts energy homeostasis, leading to negative consequences in the regulation of emotion and metabolism. Females are known to be more vulnerable to the psychological consequences of stress, such as depression and anxiety, whereas males are more vulnerable to the metabolic consequences of stress. Sex differences that exist in the susceptibility to various stress-induced disorders have led researchers to hypothesize that gonadal hormones are regulatory factors that should be considered in stress studies. Further, estrogens are heavily recognized for their protective effects on metabolic dysregulation, such as anti-obesogenic and glucose-sensing effects. Perturbations to energy homeostasis using laboratory rodents, such as physiological stress or over-/under- feeding dietary regimen prevalent in today’s society, offer hints to the underlying mechanisms of estrogenic actions. Metabolic effects of estrogens primarily work through estrogen receptor α (ERα), which is differentially expressed between the sexes in hypothalamic nuclei regulating energy metabolism and in extrahypothalamic limbic regions that are not typically associated with energy homeostasis. In this review, we discuss estrogenic actions implicated in stress-induced sex-distinct metabolic disorders. Full article
(This article belongs to the Special Issue Effects of Sex Hormones in the Regulation of Energy Metabolism in Health and Diseases)
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Other

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21 pages, 7192 KiB  
Systematic Review
The Prevalence of Hypogonadism and the Effectiveness of Androgen Administration on Body Composition in HIV-Infected Men: A Meta-Analysis
by Daniele Santi, Giorgia Spaggiari, Walter Vena, Alessandro Pizzocaro, Mario Maggi, Vincenzo Rochira and Giovanni Corona
Cells 2021, 10(8), 2067; https://doi.org/10.3390/cells10082067 - 12 Aug 2021
Cited by 13 | Viewed by 2917
Abstract
Background: Hypogonadism is a common comorbidity in human immunodeficiency virus (HIV)-infected men, although the real prevalence is difficult to be estimated. Moreover, in HIV settings, the efficacy of exogenous testosterone (Te) administration at improving body composition remains unclear. Aim of the study: This [...] Read more.
Background: Hypogonadism is a common comorbidity in human immunodeficiency virus (HIV)-infected men, although the real prevalence is difficult to be estimated. Moreover, in HIV settings, the efficacy of exogenous testosterone (Te) administration at improving body composition remains unclear. Aim of the study: This review has a double aim. First, to estimate the prevalence of pituitary–testis axis abnormality in HIV-infected patients compared to uninfected subjects. Second, to evaluate the effect of androgen administration on body composition in HIV-infected men. Materials and Methods: A systematic review of the literature and meta-analysis was carried out. Two separated literature searches were performed, the first to evaluate the prevalence of Te deficiency in HIV-infected men and the second one to evaluate effects of androgen administration on body composition. Results: The overall prevalence of Te deficiency in HIV-infected men was calculated from 41 studies, showing a 26% prevalence, which was even higher when free T (fT) levels, more than total T, were considered. Indeed, TT serum levels were similar between HIV patients and controls, although higher SHBG and lower fT were detected in HIV populations. When HIV-infected men were treated with exogenous Te, a significant increase in body weight, lean body mass and fat free mass was detected. Conclusion: The systematic review confirms the high prevalence of Te deficiency in HIV-infected men, particularly when fT has been considered. Moreover, chronic androgen supplementation improves body composition, affecting the lean mass compartment. However, considering the general frailty of HIV patients, a tailored indication for Te therapy should be advocated. Full article
(This article belongs to the Special Issue Effects of Sex Hormones in the Regulation of Energy Metabolism in Health and Diseases)
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