Adipocyte epigenetic alterations and potential therapeutic targets in transgenerationally inherited lean and obese phenotypes following ancestral exposures

King, Stephanie E.; Nilsson, Eric; Beck, Daniel; Skinner, Michael K.

doi:10.1080/21623945.2019.1693747

Cited by 18 publications

(19 citation statements)

References 110 publications

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“…This is partly in accordance with Bravo’s study from 2017, where higher levels of 4,4 DDT (4,4 DDE composed >90% of the DDT metabolites in the study [ 13 ]; the same proportion as in our material) were found to increase gestational age as well as birth weight and length. Bravo’s findings are supported by laboratory studies showing that DDT exposure increased adipogenesis in vitro [ 19 ] and obesity in rats [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 80%

Serum Concentrations of Selected Organochlorines in Pregnant Women and Associations with Pregnancy Outcomes. A Cross-Sectional Study from Two Rural Settings in Cambodia

Steinholt

Ha³

et al. 2020

IJERPH

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We conducted a cross-sectional study among 194 pregnant women from two low-income settings in Cambodia. The inclusion period lasted from October 2015 through December 2017. Maternal serum samples were analyzed for persistent organic pollutants (POPs). The aim was to study potential effects on birth outcomes. We found low levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCP), except for heptachlors, β-hexachlorocyclohexane (HCH), heptachlor epoxide, and p,p’-DDE. There were few differences between the two study locations. However, the women from the poorest areas had significantly higher concentrations of p,p’-DDE (p < 0.001) and hexachlorobenzene (HCB) (p = 0.002). The maternal factors associated with exposure were parity, age, residential area, and educational level. Despite low maternal levels of polychlorinated biphenyls, we found significant negative associations between the PCB congeners 99 (95% CI: −2.51 to −0.07), 138 (95% CI: −1.28 to −0.32), and 153 (95% CI: −1.06 to −0.05) and gestational age. Further, there were significant negative associations between gestational age, birth length, and maternal levels of o,p’-DDE. Moreover, o,p’-DDD had positive associations with birth weight, and both p,p’-DDD and o,p’-DDE were positively associated with the baby’s ponderal index. The poorest population had higher exposure and less favorable outcomes.

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Section: Discussionmentioning

confidence: 80%

Serum Concentrations of Selected Organochlorines in Pregnant Women and Associations with Pregnancy Outcomes. A Cross-Sectional Study from Two Rural Settings in Cambodia

Steinholt

Ha³

et al. 2020

IJERPH

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“…It has been proposed that the effects of DDT exposure in adipocytes on the offspring from DDT-exposed rats may be significantly mediated by DNA methylation changes affecting adipogenesis regulation and metabolic functioning [86].…”

Section: Dichlorodiphenyltrichloroethane (Ddt)mentioning

confidence: 99%

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Aaseth

Javorac

Djordjevic

et al. 2022

Toxics

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Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.

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“…Epigenetic mechanisms regulate chromatin structure and gene expression patterns which impact DNA/RNA methylation, and histone changes can modulate host immune responsiveness 75 . Obesity drives DNA methylation of differential regions in adipocytes 76 . Whether viral pathogens (e.g., influenza and SARS‐CoV‐2) trigger type I IFN axis responses in adipocytes and impact adipocyte DNA methylation remains to be defined.…”

Section: Adipocyte Functionmentioning

confidence: 99%

Greasing the inflammatory pathogenesis of viral pneumonias in diabetes

et al. 2022

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Type 2 diabetes (T2D) and obesity are independent risk factors for increased morbidity and mortality associated with influenza and SARS-CoV-2 infection. Skewed cellular metabolism shapes immune cell inflammatory responsiveness and function in obesity, T2D, and infection. However, altered immune cell responsiveness and levels of systemic proinflammatory mediators, partly independent of peripheral immune cell contribution, are linked with SARS-CoV-2-associated disease severity. Despite such knowledge, the role of tissue parenchymal cell-driven inflammatory responses, and specifically those dominantly modified in obesity (e.g., adipocytes), in influenza and SARS-CoV-2 infection pathogenesis remain poorly defined. Whether obesitydependent skewing of adipocyte cellular metabolism uncovers inflammatory clades and promotes the existence of a 'pathogenic-inflammatory' adipocyte phenotype that amplifies SARS-CoV-2 infection diseases severity in individuals with obesity and individuals with obesity and T2D has not been examined. Here, using the knowledge gained from studies of immune cell responses in obesity, T2D, and infection, we highlight the key knowledge gaps underlying adipocyte cellular functions that may sculpt and grease pathogenic processes associated with influenza and SARS-CoV-2 disease severity in diabetes.

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Adipocyte epigenetic alterations and potential therapeutic targets in transgenerationally inherited lean and obese phenotypes following ancestral exposures

Cited by 18 publications

References 110 publications

Serum Concentrations of Selected Organochlorines in Pregnant Women and Associations with Pregnancy Outcomes. A Cross-Sectional Study from Two Rural Settings in Cambodia

Serum Concentrations of Selected Organochlorines in Pregnant Women and Associations with Pregnancy Outcomes. A Cross-Sectional Study from Two Rural Settings in Cambodia

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Greasing the inflammatory pathogenesis of viral pneumonias in diabetes

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