Developmental and Transmittable Origins of Obesity-Associated Health Disorders

• Published in: Trends in genetics Vol. 33; no. 6; pp. 399 - 407
• Main Authors: Oestreich, Arin K., Moley, Kelle H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2017
• Subjects: Cardiovascular Diseases - complications; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Epigenesis, Genetic; Humans; Medical Education; Metabolic Diseases - complications; Metabolic Diseases - genetics; Metabolic Diseases - metabolism; Obesity - complications; Obesity - genetics; Obesity - metabolism
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2017.03.008

The current global obesity pandemic is clearly linked to both the increasing prevalence of, and preference for, foods high in calories, specifically fat and sucrose, and declining levels of daily physical activity. A less commonly discussed possible explanation is that risk of obesity begins in utero as a result of developmental plasticity during early life. This idea fits into the broader Developmental Origins of Health and Diseases (DOHAD) hypothesis, which holds that stressful in utero exposure manifests as disease in adulthood. In this review, we highlight several studies that have revealed the role of epigenetics in multigenerational transmission of developmentally programmed obesity and associated cardiometabolic disease. Studies performed in both rodents and humans suggest that adverse maternal conditions during the pre- and perinatal period can cause long-term transgenerational epigenetic modifications in the offspring that mediate susceptibility to cardiometabolic disease. An adverse maternal environment exposes three generations and is transmitted epigenetically through the germline only if the F3 offspring are affected. Rare regulatory sequences that escape systematic DNA demethylation and others that are able to maintain histone marks in the primordial germ cells represent a potential mechanism for non-imprinted transgenerational epigenetic inheritance. Inheritance of damaged oocyte mitochondria is an important potential transgenerational mechanism to consider because they are passed exclusively from the mother and contain mitochondrial DNA subject to epigenetic regulation.