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      Early-life nutrition and metabolic disorders in later life: a new perspective on energy metabolism

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          Abstract

          Type 2 diabetes mellitus and metabolic disorders have become an epidemic globally. However, the pathogenesis remains largely unclear and the prevention and treatment are still limited. In addition to environmental factors during adulthood, early life is the critical developmental window with high tissue plasticity, which might be modified by external environmental cues. Substantial evidence has demonstrated the vital role of early-life nutrition in programming the metabolic disorders in later life. In this review, we aim to overview the concepts of fetal programming and investigate the effects of early-life nutrition on energy metabolism in later life and the potential epigenetic mechanism. The related studies published on PubMed database up to March 2020 were included. The results showed that both maternal overnutrition and undernutrition increased the riskes of metabolic disorders in offspring and epigenetic modifications, including DNA methylation, miRNAs, and histone modification, might be the vital mediators. The beneficial effects of early-life lifestyle modifications as well as dietary and nutritional interventions on these deleterious metabolic remolding were initially observed. Overall, characterizing the early-life malnutrition that reshapes metabolic disease trajectories may yield novel targets for early prevention and intervention and provide a new point of view to the energy metabolism.

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          Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

          Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone.
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            The thrifty phenotype hypothesis.

            The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of type 2 diabetes and the metabolic syndrome result from the effects of poor nutrition in early life, which produces permanent changes in glucose-insulin metabolism. These changes include reduced capacity for insulin secretion and insulin resistance which, combined with effects of obesity, ageing and physical inactivity, are the most important factors in determining type 2 diabetes. Since the hypothesis was proposed, many studies world-wide have confirmed the initial epidemiological evidence, although the strength of the relationships has varied from one study to another. The relationship with insulin resistance is clear at all ages studied. Less clear is the relationship with insulin secretion. The relative contribution of genes and environment to these relationships remains a matter of debate. The contributions of maternal hyperglycaemia and the trajectory of postnatal growth need to be clarified.
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              Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis.

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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CM9
                Chinese Medical Journal
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0366-6999
                2542-5641
                20 August 2020
                20 August 2020
                : 133
                : 16
                : 1961-1970
                Affiliations
                Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
                Author notes
                Correspondence to: Prof. Xin-Hua Xiao, Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, ChinaE-Mail: xiaoxh2014@ 123456vip.163.com
                Article
                CMJ-2020-325 00010
                10.1097/CM9.0000000000000976
                7462214
                32826460
                e31c54d9-2fc6-4335-a25a-9a41b6377bf7
                Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 15 February 2020
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                Review Articles
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                early-life nutrition,energy metabolism,epigenetics,in later life

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