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Developmental Biology - Premature Epigenome Aging|
Our Western Diet Ages Us
"This study shows us how environmental exposures affect our health and disease susceptibility, both early and later in life.
Read all the details of this work in Nature Communications.
While these findings are only in lab model animals at this time, researchers hope this and similar studies being conducted by the TARGET II Consortium lead the way to identifying biomarkers which more precisely predict those at risk for metabolic dysfunction — described as fatty liver disease, diabetes and/or heart disease, and allow for more precise and early intervention.
This work was featured as the June paper of the month by the National Institute of Environmental Health Sciences (NIEHS).
Our early-life environment has a profound influence on developing organs that impacts metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life chemical exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome: environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.
Lindsey S. Treviño, Jianrong Dong, Ahkilesh Kaushal, Tiffany A. Katz, Rahul Kumar Jangid, Matthew J. Robertson, Sandra L. Grimm, Chandra Shekar R. Ambati, Vasanta Putluri, Aaron R. Cox, Kang Ho Kim, Thaddeus D. May, Morgan R. Gallo, David D. Moore, Sean M. Hartig, Charles E. Foulds, Nagireddy Putluri, Cristian Coarfa & Cheryl Lyn Walker.
This work was supported in part by NIH grants U01ES026719, 1P30ES030285, and R01ES023206 to CLW, American Diabetes Association grant #1-18-IBS-105 and NIH grant R01DK114356 to S.M.H., and a subaward from NIH grant U24DK097748 to C.E.F. Lipidomics and metabolomics sample processing and analysis were conducted by the Metabolomics Core at Baylor College of Medicine, supported by CPRIT Proteomics and Metabolomics Core Facility funding (RP170005), the NIH (P30 CA125123), and the Dan L. Duncan Cancer Center at Baylor College of Medicine. ChIP-sequencing and RNA-sequencing were conducted by the MD Anderson Cancer Center Science Park Next Generation Sequencing Core, supported by CPRIT Core Facility Support grants (RP120348 and RP170002). Figure 1a was created with Biorender.com.
The work was supported as part of the NIEHS multi-phased Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) Program.
The authors declare no competing interests.
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Neonatal exposure to several endocrine-disrupting chemicals or EDCs are shown to cause adult metabolic diseases as well as liver dysfunction in pre-natal organ development. CREDIT Pinterest.