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Multigenerational metabolic disruption: Developmental origins and mechanisms of propagation across generations.

ABSTRACT: It has been long known that the environment plays a critical role in the etiology of disease. However, it is still unclear how the large variety of environmental factors humans are exposed to interact with each other to lead to disease. Metabolic disorders are just one example of human disorders that have been associated with environmental exposures. Obesity and type 2 diabetes have become a health and economic burden worldwide as the number of affected people has tripled in the last 40 years. Animal and human studies have shown a strong association between exposure to environmental chemicals during critical windows of susceptibility such as periconception, prenatal, and early life, whose effect can persist through development and across generations. However, little is known about the mechanisms driving this persistence. Here, we review historical and current knowledge on the effect of exposure to environmental factors during in utero development and discuss mechanisms for these disorders to be propagated across generations.

SUBMITTER: Davis DD

PROVIDER: S-EPMC9437310 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Multigenerational metabolic disruption: Developmental origins and mechanisms of propagation across generations.

Davis Daniel D DD Diaz-Castillo Carlos C Chamorro-Garcia Raquel R

Frontiers in toxicology 20220819

It has been long known that the environment plays a critical role in the etiology of disease. However, it is still unclear how the large variety of environmental factors humans are exposed to interact with each other to lead to disease. Metabolic disorders are just one example of human disorders that have been associated with environmental exposures. Obesity and type 2 diabetes have become a health and economic burden worldwide as the number of affected people has tripled in the last 40 years. A ...[more]

PMID: 36060120

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Project description:Although polychlorinated biphenyls and polybrominated biphenyls are no longer manufactured the United States, biomonitoring in human populations show that exposure to these pollutants persist in human tissues. The objective of this study was to identify metabolic variations associated with exposure to 2,2'4,4',5,5'-hexabromobiphenyl (PBB-153) and 2,2'4,4',5,5'-hexachlorobiphenyl (PCB-153) in two generations of participants enrolled in the Michigan PBB Registry (http://pbbregistry.emory.edu/). Untargeted, high-resolution metabolomic profiling of plasma collected from 156 individuals was completed using liquid chromatography with high-resolution mass spectrometry. PBB-153 and PCB-153 levels were measured in the same individuals using targeted gas chromatography-tandem mass spectrometry and tested for dose-dependent correlation with the metabolome. Biological response to these exposures were evaluated using identified endogenous metabolites and pathway enrichment. When compared to lipid-adjusted concentrations for adults in the National Health and Nutrition Examination Survey (NHANES) for years 2003-2004, PCB-153 levels were consistent with similarly aged individuals, whereas PBB-153 concentrations were elevated (p<0.0001) in participants enrolled in the Michigan PBB Registry. Metabolic alterations were correlated with PBB-153 and PCB-153 in both generations of participants, and included changes in pathways related to catecholamine metabolism, cellular respiration, essential fatty acids, lipids and polyamine metabolism. These pathways were consistent with pathophysiological changes observed in neurodegenerative disease and included previously identified metabolomic markers of Parkinson's disease. To determine if the metabolic alterations detected in this study are replicated other cohorts, we evaluated correlation of PBB-153 and PCB-153 with plasma fatty acids measured in NHANES. Both pollutants showed similar associations with fatty acids previously linked to PCB exposure. Thus, the results from this study show metabolic alterations correlated with PBB-153 and PCB-153 exposure can be detected in human populations and are consistent with health outcomes previously reported in epidemiological and mechanistic studies.

Dataset Information

Multigenerational metabolic disruption: Developmental origins and mechanisms of propagation across generations.

Publications

Multigenerational metabolic disruption: Developmental origins and mechanisms of propagation across generations.

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