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  1. Article ; Online: Metabolic dysfunction in polycystic ovary syndrome

    Miguel A. Sanchez-Garrido / Manuel Tena-Sempere

    Molecular Metabolism, Vol 35, Iss , Pp - (2020)

    Pathogenic role of androgen excess and potential therapeutic strategies

    2020  

    Abstract: Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display ... ...

    Abstract Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited. Scope of review: This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions. Major conclusions: Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome. Keywords: PCOS, Androgen ...
    Keywords Internal medicine ; RC31-1245
    Subject code 570
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Author Correction

    Francisco Gaytan / Concepción Morales / Carlos Reymundo / Manuel Tena-Sempere

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    A novel RGB-trichrome staining method for routine histological analysis of musculoskeletal tissues

    2021  Volume 1

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases

    Jose Antonio Santos-Marcos / Marina Mora-Ortiz / Manuel Tena-Sempere / Jose Lopez-Miranda / Antonio Camargo

    Biology of Sex Differences, Vol 14, Iss 1, Pp 1-

    2023  Volume 24

    Abstract: Highlights Accumulating evidences show that the alterations in the gut microbiota associated to metabolic diseases are different in men and women, and these differences may influence sex differences in the development and prevalence of metabolic diseases. ...

    Abstract Highlights Accumulating evidences show that the alterations in the gut microbiota associated to metabolic diseases are different in men and women, and these differences may influence sex differences in the development and prevalence of metabolic diseases. The key aspects involved in these pathologies include lipopolysaccharide-inflammation, gut barrier integrity, gut microbiota-derived metabolites and gut–brain axis. Sex steroids, mainly estrogen and testosterone, are thought to play a prominent role in the sexual dimorphism of gut microbiota. The influence of sex hormones is reflected both in men and women, and among women themselves due to hormonal changes associated with the menopause. The interaction between sex steroids and the gut microbiota plays a prominent role in the development of metabolic diseases.
    Keywords Gut microbiota ; Sex steroids ; Sex differences ; Obesity ; Metabolic syndrome ; Type 2 diabetes ; Medicine ; R ; Physiology ; QP1-981
    Subject code 360
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity

    Daniela Fernandois / María Jesús Vázquez / Alexia Barroso / Alfonso H. Paredes / Manuel Tena-Sempere / Gonzalo Cruz

    International Journal of Molecular Sciences, Vol 24, Iss 23, p

    2023  Volume 16909

    Abstract: Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The ... ...

    Abstract Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.
    Keywords leptin ; norepinephrine ; sympathetic nervous system ; ovary ; liver ; fat ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A novel RGB-trichrome staining method for routine histological analysis of musculoskeletal tissues

    Francisco Gaytan / Concepción Morales / Carlos Reymundo / Manuel Tena-Sempere

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Morphometry and histology are essential approaches for investigation and diagnosis of musculo-skeletal disorders. Despite the advent of revolutionary methods of image analysis and high resolution three-dimensional imaging technology, basic ... ...

    Abstract Abstract Morphometry and histology are essential approaches for investigation and diagnosis of musculo-skeletal disorders. Despite the advent of revolutionary methods of image analysis and high resolution three-dimensional imaging technology, basic conventional light microscopy still provides an incisive overview of the structure and tissue dynamics of the musculoskeletal system. This is crucial to both preclinical and clinical research, since several clinically relevant processes, such as bone repair, osteoarthritis, and metabolic bone diseases, display distinct, if not pathognomonic, histological features. Due to the particular characteristics of the skeletal tissues (i.e., the existence of mineralized extracellular matrices), a large number of staining methods applicable to either decalcified or undecalcified tissues are available. However, it is usually the case that several staining methods need to be sequentially applied in order to achieve the different endpoints required to fully assess skeletal tissue structure and dynamics, and to allow morphometric quantification. We describe herein a novel staining method, the RGB trichrome, amenable for application to decalcified, paraffin embedded human musculoskeletal tissues. The acronym RGB corresponds to the three primary dyes used: picrosirius Red, fast Green, and alcian Blue. Although these individual pigments are commonly used either isolated, in binary combinations, or as part of more complex polychrome staining methods, when merged in the RGB trichrome staining produce high-quality/high-contrast images, permitting not only clear identification of different tissues (i.e., the different types of cartilage, bone and fibrous connective tissue), but also discrimination between calcified and uncalcified bone and cartilage, as well as an unexpected diversity of shades of color, while displaying singular properties among polychrome staining methods, such as the unveiling of the bone osteocyte dendritic/canalicular network. Hence, we propose the RGB trichrome as simple but highly-reliable tool for the preclinical and clinical study of the musculoskeletal system.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Connecting metabolism and reproduction: Roles of central energy sensors and key molecular mediators

    Roa, Juan / Manuel Tena-Sempere

    Molecular and cellular endocrinology. 2014,

    2014  

    Abstract: It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy ... ...

    Abstract It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease.
    Keywords body weight ; brain ; energy balance ; ghrelin ; gonads ; homeostasis ; insulin ; leptin ; metabolism ; neuropeptides ; puberty ; reproduction
    Language English
    Size p. .
    Publishing place Elsevier Ireland Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2014.09.027
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: The long-lasting shadow of litter size in rodents

    Marcela Parra-Vargas / Sebastien G. Bouret / Jens C. Bruning / Egberto G. de Moura / Theodore Garland, Jr. / Patricia C. Lisboa / Susan E. Ozanne / Mary-Elizabeth Patti / Andreas Plagemann / John R. Speakman / Manuel Tena-Sempere / Catherine Vergely / Lori M. Zeltser / Josep C. Jiménez-Chillarón

    Molecular Metabolism, Vol 71, Iss , Pp 101707- (2023)

    litter size is an underreported variable that strongly determines adult physiology

    2023  

    Abstract: Background/Purpose: Litter size is a biological variable that strongly influences adult physiology in rodents. Despite evidence from previous decades and recent studies highlighting its major impact on metabolism, information about litter size is ... ...

    Abstract Background/Purpose: Litter size is a biological variable that strongly influences adult physiology in rodents. Despite evidence from previous decades and recent studies highlighting its major impact on metabolism, information about litter size is currently underreported in the scientific literature. Here, we urge that this important biological variable should be explicitly stated in research articles. Results/Conclusion: Below, we briefly describe the scientific evidence supporting the impact of litter size on adult physiology and outline a series of recommendations and guidelines to be implemented by investigators, funding agencies, editors in scientific journals, and animal suppliers to fill this important gap.
    Keywords Litter size reduction ; Neonatal growth ; Childhood obesity ; Experimental models of physiology ; Internal medicine ; RC31-1245
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin

    María J. Vázquez / Marta G. Novelle / Francisca Rodríguez-Pacheco / Ricardo Lage / Luis Varela / Miguel López / Leonor Pinilla / Manuel Tena-Sempere / Carlos Diéguez

    Cells, Vol 9, Iss 1940, p

    2020  Volume 1940

    Abstract: GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution ... ...

    Abstract GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone–releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo.
    Keywords AMPK ; GH ; GHRH ; ghrelin ; hypothalamic signaling ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Crowding and Follicular Fate

    Francisco Gaytan / Concepcion Morales / Silvia Leon / David Garcia-Galiano / Juan Roa / Manuel Tena-Sempere

    PLoS ONE, Vol 10, Iss 12, p e

    Spatial Determinants of Follicular Reserve and Activation of Follicular Growth in the Mammalian Ovary.

    2015  Volume 0144099

    Abstract: Initiation of growth of resting ovarian follicles is a key phenomenon for providing an adequate number of mature oocytes in each ovulation, while preventing premature exhaustion of primordial follicle reserve during the reproductive lifespan. Resting ... ...

    Abstract Initiation of growth of resting ovarian follicles is a key phenomenon for providing an adequate number of mature oocytes in each ovulation, while preventing premature exhaustion of primordial follicle reserve during the reproductive lifespan. Resting follicle dynamics strongly suggest that primordial follicles are under constant inhibitory influences, by mechanisms and factors whose nature remains ill defined. In this work, we aimed to assess the influence of spatial determinants, with special attention to clustering patterns and crowding, on the fate of early follicles in the adult mouse and human ovary. To this end, detailed histological and morphometric analyses, targeting resting and early growing follicles, were conducted in ovaries from mice, either wild type (WT) or genetically modified to lack kisspeptin receptor expression (Kiss1r KO), and healthy adult women. Kiss1r KO mice were studied as model of persistent hypogonadotropism and anovulation. Different qualitative and quantitative indices of the patterns of spatial distribution of resting and early growing follicles in the mouse and human ovary, including the Morisita's index of clustering, were obtained. Our results show that resting primordial follicles display a clear-cut clustered pattern of spatial distribution in adult mouse and human ovaries, and that resting follicle aggrupation is inversely correlated with the proportion of follicles initiating growth and entering into the growing pool. As a whole, our data suggest that resting follicle crowding, defined by changes in density and clustered pattern of distribution, is a major determinant of follicular activation and the fate of ovarian reserve. Uneven follicle crowding would constitute the structural counterpart of the major humoral regulators of early follicular growth, with potential implications in ovarian ageing and pathophysiology.
    Keywords Medicine ; R ; Science ; Q
    Subject code 910
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice

    Juan Roa / Miguel Ruiz-Cruz / Francisco Ruiz-Pino / Rocio Onieva / Maria J. Vazquez / Maria J. Sanchez-Tapia / Jose M. Ruiz-Rodriguez / Veronica Sobrino / Alexia Barroso / Violeta Heras / Inmaculada Velasco / Cecilia Perdices-Lopez / Claes Ohlsson / Maria Soledad Avendaño / Vincent Prevot / Matti Poutanen / Leonor Pinilla / Francisco Gaytan / Manuel Tena-Sempere

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 19

    Abstract: Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of ... ...

    Abstract Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.
    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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