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.
    International Journal of Endocrinology 10/2015; 2015(2):1-17. DOI:10.1155/2015/949085 · 1.95 Impact Factor
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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.
    Reviews in Endocrine and Metabolic Disorders 09/2013; 14(4). DOI:10.1007/s11154-013-9263-7 · 4.89 Impact Factor
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    • "There is a wealth of clinical and experimental data demonstrating that sex steroids and insulin interact in their effects on several tissues [33]. The deficiency of estrogens or its receptors is associated with increased adiposity, in particular in visceral fat, which impairs insulin sensitivity [17], [34]. Moreover, restoration of estrogens levels in ovariectomized mice blunts the body weight gain. "
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    ABSTRACT: Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat) for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77.
    PLoS ONE 01/2013; 8(1):e53836. DOI:10.1371/journal.pone.0053836 · 3.23 Impact Factor
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