Sexual differences in the control of energy homeostasis

Obesity Research Center, University of Cincinnati, Cincinnati, OH, USA.
Frontiers in Neuroendocrinology (Impact Factor: 7.58). 04/2009; 30(3):396-404. DOI: 10.1016/j.yfrne.2009.03.004
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Haifei Shi, Aug 01, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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 · 3.81 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "Furthermore, and especially important for understanding the pathogenesis of obesity and its metabolic complications, interactions of sex differences in gene expression with environmental variables such as diet composition and exercise/activity on fatness and fat distribution remain largely unexplored. Because excellent reviews of sex differences in the regulation of food intake and body weight have been recently published [6,7], in this review, we focus on physiologic and genetic determinants of sex differences in fat distribution. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.
    05/2012; 3(1):13. DOI:10.1186/2042-6410-3-13
Show more