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      The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility

      review-article
      1 , 2 , 1 , 3 , *
      Nutrients
      MDPI
      fertility, reproduction, women, energy metabolism, nutrients

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          Abstract

          In female mammals, mechanisms have been developed, throughout evolution, to integrate environmental, nutritional and hormonal cues in order to guarantee reproduction in favorable energetic conditions and to inhibit it in case of food scarcity. This metabolic strategy could be an advantage in nutritionally poor environments, but nowadays is affecting women’s health. The unlimited availability of nutrients, in association with reduced energy expenditure, leads to alterations in many metabolic pathways and to impairments in the finely tuned inter-relation between energy metabolism and reproduction, thereby affecting female fertility. Many energetic states could influence female reproductive health being under- and over-weight, obesity and strenuous physical activity are all conditions that alter the profiles of specific hormones, such as insulin and adipokines, thus impairing women fertility. Furthermore, specific classes of nutrients might affect female fertility by acting on particular signaling pathways. Dietary fatty acids, carbohydrates, proteins and food-associated components (such as endocrine disruptors) have per se physiological activities and their unbalanced intake, both in quantitative and qualitative terms, might impair metabolic homeostasis and fertility in premenopausal women. Even though we are far from identifying a “fertility diet”, lifestyle and dietary interventions might represent a promising and invaluable strategy to manage infertility in premenopausal women.

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          The mechanisms of action of PPARs.

          The peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, PPAR gamma, PPAR alpha, and PPAR delta, encoded by different genes. PPARs are ligand-regulated transcription factors that control gene expression by binding to specific response elements (PPREs) within promoters. PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors such that the rate of transcription initiation is increased. The PPARs play a critical physiological role as lipid sensors and regulators of lipid metabolism. Fatty acids and eicosanoids have been identified as natural ligands for the PPARs. More potent synthetic PPAR ligands, including the fibrates and thiazolidinediones, have proven effective in the treatment of dyslipidemia and diabetes. Use of such ligands has allowed researchers to unveil many potential roles for the PPARs in pathological states including atherosclerosis, inflammation, cancer, infertility, and demyelination. Here, we present the current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases.
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            Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase.

            The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. However, evidence that this is physiologically relevant currently only exists for LKB1. We now report that there is a significant basal activity and phosphorylation of AMPK in LKB1-deficient cells that can be stimulated by Ca2+ ionophores, and studies using the CaMKK inhibitor STO-609 and isoform-specific siRNAs show that CaMKKbeta is required for this effect. CaMKKbeta also activates AMPK much more rapidly than CaMKKalpha in cell-free assays. K(+)-induced depolarization in rat cerebrocortical slices, which increases intracellular Ca2+ without disturbing cellular adenine nucleotide levels, activates AMPK, and this is blocked by STO-609. Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta.
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              Polycystic Ovary Syndrome

              New England Journal of Medicine, 352(12), 1223-1236
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                11 February 2016
                February 2016
                : 8
                : 2
                : 87
                Affiliations
                [1 ]Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, Milan 20133, Italy; roberta.fontana@ 123456iit.it
                [2 ]Department of Drug Discovery and Development, Italian Institute of Technology, via Morego 30, Genova 16163, Italy
                [3 ]Center of Excellence of Neurodegenerative Diseases, University of Milan, via Balzaretti 9, Milan 20133, Italy
                Author notes
                [* ]Correspondence: sara.dellatorre@ 123456unimi.it ; Tel.: +39-02-5031-8405; Fax: +39-02-5031-8284
                Article
                nutrients-08-00087
                10.3390/nu8020087
                4772050
                26875986
                dded190c-e201-4b47-8909-e9cb0ab1c429
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2015
                : 02 February 2016
                Categories
                Review

                Nutrition & Dietetics
                fertility,reproduction,women,energy metabolism,nutrients
                Nutrition & Dietetics
                fertility, reproduction, women, energy metabolism, nutrients

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