Sexual differences in the control of energy homeostasis

Obesity Research Center, University of Cincinnati, Cincinnati, OH, USA.
Frontiers in Neuroendocrinology (Impact Factor: 7.04). 04/2009; 30(3):396-404. DOI: 10.1016/j.yfrne.2009.03.004
Source: PubMed


The prevalence of obesity has reached epidemic proportion with enormous costs in both human lives and healthcare dollars spent. Obesity-related metabolic disorders are much lower in premenopausal women than men; however, there is a dramatic increase following menopause in women. The health risks associated with obesity vary depending on the location of adipose tissue. Adipose tissue distributed in the abdominal visceral carry a much greater risk for metabolic disorders than does adipose tissue distributed subcutaneously. There are distinct sex-dependent differences in the regional fat distribution, women carry more fat subcutaneously whereas men carry more fat viscerally. Males and females differ with respect to their regulation of energy homeostasis. Peripheral adiposity hormones such as leptin and insulin as well as sex hormones directly influence energy balance. Sexual dimorphisms in energy balance, body fat distribution, and the role sex hormones have in mediating these differences are the focus of this review.

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Available from: Haifei Shi, Aug 01, 2014
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    • "In fact, hypothalamic inflammation with activation of microglia and astrocytes in these brain nuclei caused by high-fat diet feeding and increased body fat have been demonstrated in recent studies [97] [100] [105]. Therefore, it is logical to presume the presence of ERs in hypothalamic microglia and astrocytes to contribute to anti-inflammatory effects of estrogens and differential regulation of energy homeostasis between sexes [33] [106]. Whether ERí µí»¼ is expressed in microglia and astrocytes in the hypothalamus has been an ongoing debate. "
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    ABSTRACT: Sex differences exist in the complex regulation of energy homeostasis that utilizes central and peripheral systems. It is widely accepted that sex steroids, especially estrogens, are important physiological and pathological components in this sex-specific regulation. Estrogens exert their biological functions via estrogen receptors (ERs). ER α , a classic nuclear receptor, contributes to metabolic regulation and sexual behavior more than other ER subtypes. Physiological and molecular studies have identified multiple ER α -rich nuclei in the hypothalamus of the central nervous system (CNS) as sites of actions that mediate effects of estrogens. Much of our understanding of ER α regulation has been obtained using transgenic models such as ER α global or nuclei-specific knockout mice. A fundamental question concerning how ER α is regulated in wild-type animals, including humans, in response to alterations in steroid hormone levels, due to experimental manipulation (i.e., castration and hormone replacement) or physiological stages (i.e., puberty, pregnancy, and menopause), lacks consistent answers. This review discusses how different sex hormones affect ER α expression in the hypothalamus. This information will contribute to the knowledge of estrogen action in the CNS, further our understanding of discrepancies in correlation of altered sex hormone levels with metabolic disturbances when comparing both sexes, and improve health issues in postmenopausal women.
    Full-text · Article · Oct 2015 · International Journal of Endocrinology
    • "In humans, males and females differ dramatically in susceptibility to IR, whereby males are more prone to develop IR than females (Geer and Shen, 2009). Sex-specific distributions between visceral and subcutaneous adipose tissue depots as well as gonadal hormones are believed to be responsible in part for the dramatic sex differences in IR (Shi et al., 2009). Experimentally, females are less susceptible to fatty acidinduced peripheral IR and have increased insulin sensitivity in adipose tissue (Frias et al., 2001; Macotela et al., 2009). "
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    ABSTRACT: Insulin resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment, and disease pathology, the genetic basis of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates. Our results show dramatic variation in IR among strains of mice and widespread differences between sexes that are dependent on genotype. We uncover more than 15 genome-wide significant loci and validate a gene, Agpat5, associated with IR. We also integrate plasma metabolite levels and global gene expression from liver and adipose tissue to identify metabolite quantitative trait loci (mQTL) and expression QTL (eQTL), respectively. Our results provide a resource for analysis of interactions between diet, sex, and genetic background in IR. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · Cell Metabolism
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    • "Obesity affects males and females differently. The metabolic response to dietary regimes and pharmacological treatments for obesity differ between the sexes [3–9]. Differences in the levels of circulating gonadal steroids are critical for many of the sexually dimorphic characteristics. "
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    ABSTRACT: Obesity, and its associated comorbidities such as type 2 diabetes, cardiovascular diseases, and certain cancers, represent major health challenges. Importantly, there is a sexual dimorphism with respect to the prevalence of obesity and its associated metabolic diseases, implicating a role for gonadal hormones. Specifically, estrogens have been demonstrated to regulate metabolism perhaps by acting as a leptin mimetic in the central nervous system (CNS). CNS estrogen receptors (ERs) include ER alpha (ERα) and ER beta (ERβ), which are found in nuclear, cytoplasmic and membrane sites throughout the brain. Additionally, estrogens can bind to and activate a G protein-coupled estrogen receptor (GPER), which is a membrane-associated ER. ERs are expressed on neurons as well as glia, which are known to play a major role in providing nutrient supply for neurons and have recently received increasing attention for their potentially important involvement in the CNS regulation of systemic metabolism and energy balance. This brief overview summarizes data focusing on the potential role of astrocytic estrogen action as a key component of estrogenic modulation responsible for mediating the sexual dimorphism in body weight regulation and obesity.
    Full-text · Article · Sep 2013 · Reviews in Endocrine and Metabolic Disorders
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