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      A Guide to Applying the Sex-Gender Perspective to Nutritional Genomics

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          Abstract

          Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the different phenotypes studied, thus there is little information available on this issue and needs to be improved. Here we argue for the need to incorporate the gender perspective in nutritional genomics studies, present the general context, analyze the differences between sex and gender, as well as the limitations to measuring them and to detecting specific sex-gene or sex-phenotype associations, both at the specific gene level or in genome-wide-association studies. We analyzed the main sex-specific gene-diet interactions published to date and their main limitations and present guidelines with recommendations to be followed when undertaking new nutritional genomics studies incorporating the gender perspective.

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          Most cited references86

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          Sex differences in metabolic homeostasis, diabetes, and obesity

          There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately. These sex-specific differences in energy homeostasis and metabolic dysfunction represent an untested source of factors that can be harnessed to develop relevant sex-based therapeutic avenues for diabetes, metabolic syndrome, and obesity.
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            Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome

            The translation of the growing increase of findings emerging from basic nutritional science into meaningful and clinically relevant dietary advices represents nowadays one of the main challenges of clinical nutrition. From nutrigenomics to deep phenotyping, many factors need to be taken into account in designing personalized and unbiased nutritional solutions for individuals or population sub-groups. Likewise, a concerted effort among basic, clinical scientists and health professionals will be needed to establish a comprehensive framework allowing the implementation of these new findings at the population level. In a world characterized by an overwhelming increase in the prevalence of obesity and associated metabolic disturbances, such as type 2 diabetes and cardiovascular diseases, tailored nutrition prescription represents a promising approach for both the prevention and management of metabolic syndrome. This review aims to discuss recent works in the field of precision nutrition analyzing most relevant aspects affecting an individual response to lifestyle/nutritional interventions. Latest advances in the analysis and monitoring of dietary habits, food behaviors, physical activity/exercise and deep phenotyping will be discussed, as well as the relevance of novel applications of nutrigenomics, metabolomics and microbiota profiling. Recent findings in the development of precision nutrition are highlighted. Finally, results from published studies providing examples of new avenues to successfully implement innovative precision nutrition approaches will be reviewed.
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              Studying both sexes: a guiding principle for biomedicine.

              In May 2014, the U.S. National Institutes of Health (NIH) announced that it will ensure that investigators account for sex as a biological variable (SABV) in NIH-funded preclinical research as part of the agency's rigor and transparency initiative. Herein, I describe in more detail the rationale behind the SABV policy component and provide additional detail about policy goals. In short, studying both sexes is a guiding principle in biomedical research that will expand knowledge toward turning discovery into health. NIH expects that considering SABV in preclinical research will help to build a knowledge base that better informs the design of clinical research and trials in humans. Integrating the practice of studying both sexes in preclinical research will, over time, expand our currently incomplete knowledge base that plays a critical role in informing the development of sex- and gender-appropriate medical care for women and men.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                20 December 2018
                January 2019
                : 11
                : 1
                : 4
                Affiliations
                [1 ]CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain; oscar.coltell@ 123456uji.es (O.C.); Olga.Portoles@ 123456uv.es (O.P.); Rebeca.Fernandez@ 123456uv.es (R.F.-C.); jose.sorli@ 123456uv.es (J.V.S.)
                [2 ]Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
                [3 ]Department of Computer Languages and Systems, Universitat Jaume I, 12071 Castellón, Spain
                [4 ]School of Applied Health Sciences and Wellness, Ohio University, Athens, OH 45701, USA; sotospri@ 123456ohio.edu
                [5 ]Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; jmattei@ 123456hsph.harvard.edu
                [6 ]Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
                [7 ]Oncology Department, Sagunto Hospital, 46500 Sagunto, Spain; jbramire@ 123456uv.es
                [8 ]Ophthalmology Research Unit “Santiago Grisolia”, Dr. Peset University Hospital, 46017 Valencia, Spain; Vicente.Zanon-Moreno@ 123456uv.es
                [9 ]Red Temática de Investigación Cooperativa OftaRed, Instituto de Salud Carlos III, 28029 Madrid, Spain
                [10 ]Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 USA; jose.ordovas@ 123456tufts.edu
                [11 ]Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain
                [12 ]IMDEA Alimentación, 28049 Madrid, Spain
                Author notes
                [* ]Correspondence: Dolores.corella@ 123456uv.es ; Tel.: +34-963-86-4800
                Author information
                https://orcid.org/0000-0002-2366-4104
                https://orcid.org/0000-0002-4518-8495
                https://orcid.org/0000-0003-1179-1592
                https://orcid.org/0000-0001-5424-8245
                Article
                nutrients-11-00004
                10.3390/nu11010004
                6357147
                30577445
                c734daa6-5f01-4b90-9afb-99edecf9be2c
                © 2018 by the authors.

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

                History
                : 29 November 2018
                : 18 December 2018
                Categories
                Review

                Nutrition & Dietetics
                sex,gender,diet,nutritional genomics,nutrigenomics,precision nutrition
                Nutrition & Dietetics
                sex, gender, diet, nutritional genomics, nutrigenomics, precision nutrition

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