DNA damage, obesity and obesity-related health complications: what are new data telling us?

Abstract

Obesity is associated with increased DNA damage, which may in turn contribute to the development of obesity-related complications. DNA damage can also affect adipocyte biology, resulting in increased adiposity. Carefully managed weight loss programs can reverse this process. This article surveys new data that support these contentions. Whole exome sequencing analyses have identified rare variants linked to high BMI and adiposity. Two of the identified genes are linked to DNA damage and DNA repair, suggesting that DNA damage itself may play a role in the cause of obesity. It has also been recognized that obesity increases DNA damage in breast tissue of carriers of BRCA mutations and rates of tumour formation in BRCA1+ mice, indicating effect of obesity on cancer development in high-risk populations. In addition, obesity promotes cancer cell chemoresistance by decreasing fatty acid oxidation involved in cellular DNA damage response, leading to apoptotic cellular death. Obesity is also associated with a reduced capacity of oocytes to repair sperm DNA damage, leading to lower in-vitro fertilization rates in women with obesity. DNA damage and cellular responses to DNA damage can be both the result and the cause of obesity and can strongly influence the development and treatment of obesity-associated diseases.