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      Progress in the molecular understanding of central regulation of body weight by estrogens

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          Abstract

          Objective

          Estrogens can act in the brain to prevent body weight gain. Tremendous research efforts have been focused on estrogen physiology in the brain in the context of body weight control; estrogen receptors and the related signals have been attractive targets for development of new obesity therapies. The objective is to review recent findings in these aspects.

          Methods

          We reviewed recent studies, primarily from those using the conventional and conditional knockout mouse strains, regarding the cellular and molecular mechanisms for the beneficial effects of estrogens on body weight balance. We also discuss emerging genetic tools that could further benefit the field of estrogen research, and newly developed estrogen-based regimen that produce body weight-lowering benefits.

          Results

          The body weight-lowering effects of estrogens are mediated by multiple forms of estrogen receptors, in different brain regions through distinct but coordinated mechanisms. Both rapid signals and “classic” nuclear receptor actions of estrogen receptors appear to contribute to estrogenic regulation on body weight.

          Conclusion

          Estrogen receptors and associated signal networks are potential targets for obesity treatment, and further investigations are warranted.

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          Most cited references54

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          Anatomy and regulation of the central melanocortin system.

          Roger Cone (2005)
          The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
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            Sex differences in the physiology of eating.

            Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.
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              From lesions to leptin: hypothalamic control of food intake and body weight.

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                Author and article information

                Journal
                101264860
                32902
                Obesity (Silver Spring)
                Obesity (Silver Spring)
                Obesity (Silver Spring, Md.)
                1930-7381
                1930-739X
                6 March 2015
                10 April 2015
                May 2015
                01 May 2016
                : 23
                : 5
                : 919-926
                Affiliations
                [1 ]Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030
                [2 ]Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030
                Author notes
                [* ]Correspondence should be addressed to: Yong Xu, 1100 Bates Street, Rm 8070, Houston, Texas 77030. yongx@ 123456bcm.edu , Telephone: (713)-798-7199, Fax: (713)-798-7187
                Article
                NIHMS669409
                10.1002/oby.21099
                4414873
                25865677
                63cfe3b5-4512-4c9b-a8a4-6cd49317dd78

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