The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception
Understanding the developmental origins of health and disease is integral to overcome the global tide of obesity and its metabolic consequences, including atherosclerotic cardiovascular disease, type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease. The rising prevalence of obesity h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1032491/full |
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| author | Ananthi Rajamoorthi Charles A. LeDuc Charles A. LeDuc Vidhu V. Thaker Vidhu V. Thaker Vidhu V. Thaker |
| author_facet | Ananthi Rajamoorthi Charles A. LeDuc Charles A. LeDuc Vidhu V. Thaker Vidhu V. Thaker Vidhu V. Thaker |
| author_sort | Ananthi Rajamoorthi |
| collection | DOAJ |
| description | Understanding the developmental origins of health and disease is integral to overcome the global tide of obesity and its metabolic consequences, including atherosclerotic cardiovascular disease, type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease. The rising prevalence of obesity has been attributed, in part, to environmental factors including the globalization of the western diet and unhealthy lifestyle choices. In this review we argue that how and when such exposures come into play from conception significantly impact overall risk of obesity and later health outcomes. While the laws of thermodynamics dictate that obesity is caused by an imbalance between caloric intake and energy expenditure, the drivers of each of these may be laid down before the manifestation of the phenotype. We present evidence over the last half-century that suggests that the temporospatial evolution of obesity from intrauterine life and beyond is, in part, due to the conditioning of physiological processes at critical developmental periods that results in maladaptive responses to obesogenic exposures later in life. We begin the review by introducing studies that describe an association between perinatal factors and later risk of obesity. After a brief discussion of the pathogenesis of obesity, including the systemic regulation of appetite, adiposity, and basal metabolic rate, we delve into the mechanics of how intrauterine, postnatal and early childhood metabolic environments may contribute to adult obesity risk through the process of metabolic conditioning. Finally, we detail the specific epigenetic pathways identified both in preclinical and clinical studies that synergistically “program” obesity. |
| first_indexed | 2024-04-13T23:29:01Z |
| format | Article |
| id | doaj.art-7d71b71dedea43be9217271b6e261eb3 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T23:29:01Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-7d71b71dedea43be9217271b6e261eb32022-12-22T02:24:58ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.10324911032491The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conceptionAnanthi Rajamoorthi0Charles A. LeDuc1Charles A. LeDuc2Vidhu V. Thaker3Vidhu V. Thaker4Vidhu V. Thaker5Department of Pediatrics, Columbia University Medical Center, New York, NY, United StatesDepartment of Pediatrics, Columbia University Medical Center, New York, NY, United StatesThe Naomi Berrie Diabetes Center, Columbia University IRVING Medical Center, New York, NY, United StatesDepartment of Pediatrics, Columbia University Medical Center, New York, NY, United StatesThe Naomi Berrie Diabetes Center, Columbia University IRVING Medical Center, New York, NY, United StatesVagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesUnderstanding the developmental origins of health and disease is integral to overcome the global tide of obesity and its metabolic consequences, including atherosclerotic cardiovascular disease, type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease. The rising prevalence of obesity has been attributed, in part, to environmental factors including the globalization of the western diet and unhealthy lifestyle choices. In this review we argue that how and when such exposures come into play from conception significantly impact overall risk of obesity and later health outcomes. While the laws of thermodynamics dictate that obesity is caused by an imbalance between caloric intake and energy expenditure, the drivers of each of these may be laid down before the manifestation of the phenotype. We present evidence over the last half-century that suggests that the temporospatial evolution of obesity from intrauterine life and beyond is, in part, due to the conditioning of physiological processes at critical developmental periods that results in maladaptive responses to obesogenic exposures later in life. We begin the review by introducing studies that describe an association between perinatal factors and later risk of obesity. After a brief discussion of the pathogenesis of obesity, including the systemic regulation of appetite, adiposity, and basal metabolic rate, we delve into the mechanics of how intrauterine, postnatal and early childhood metabolic environments may contribute to adult obesity risk through the process of metabolic conditioning. Finally, we detail the specific epigenetic pathways identified both in preclinical and clinical studies that synergistically “program” obesity.https://www.frontiersin.org/articles/10.3389/fendo.2022.1032491/fullchildhood obesitymetabolic programingepigeneticsin utero environmentcardiometabolic riskpostnatal conditions |
| spellingShingle | Ananthi Rajamoorthi Charles A. LeDuc Charles A. LeDuc Vidhu V. Thaker Vidhu V. Thaker Vidhu V. Thaker The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception Frontiers in Endocrinology childhood obesity metabolic programing epigenetics in utero environment cardiometabolic risk postnatal conditions |
| title | The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception |
| title_full | The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception |
| title_fullStr | The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception |
| title_full_unstemmed | The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception |
| title_short | The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that “program” obesity from conception |
| title_sort | metabolic conditioning of obesity a review of the pathogenesis of obesity and the epigenetic pathways that program obesity from conception |
| topic | childhood obesity metabolic programing epigenetics in utero environment cardiometabolic risk postnatal conditions |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1032491/full |
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