In a 2018 Journal of Physiology Paper, TPLH & Mexican National Institutes of Health Researchers Establish Genetic Changes to Offspring of Obese Mothers that Predispose to Liver Disease
It is now well accepted that the offspring of obese mothers are themselves predisposed to obesity. This process is called developmental programming, by which the environment experienced during development alters the overall nature of an individual’s metabolism with potential adverse consequences. While programming of offspring obesity by maternal obesity has been a matter of intense investigation over the last 10 years in many experimental species, there is very little information on how exposure to the environment in an obese pregnancy alters gene expression in offspring. To address the literature gap, TPLH published a paper in the Journal of Physiology in collaboration with a group led by Dr. Elena Zambrano at the National Institutes of Health in Mexico City. We showed that in young adult rats at an age equivalent to about 25 years in humans the activity of genes in the liver was greatly modified in the offspring of obese mothers in a way that showed similar gene changes to those seen in the human liver in early diabetes and non-alcoholic fatty liver disease. The changes were much more marked in the livers of males than in females, showing the development of programming differs in the two sexes.
Given the current explosion of childhood obesity these data will be of value in suggesting diagnostic and therapeutic measures to prevent the unwanted outcomes of childhood obesity. One other interesting observation was that the livers of offspring of obese mothers showed changes in genes that are known to play a role in liver cancer. We are pursuing this interesting observation since developmental programming of cancer is one of the least explored aspects of programming compared with other outcomes such as cardiovascular and neurological dysfunction, obesity, diabetes, and neuroendocrine and renal disease.
Male (A) and female (B) principle component analysis from total genes mapped, Venn diagram from up- and down- differentially expressed genes in maternal obesity vs. control (C), male (D) and female (E) heat map of differentially expressed genes, and male (F) and female (G) GO biological process analysis. The heat maps correspond to one sample for each column and one gene for each horizontal line and represent all DEGs, for males 1365 and for females 70. Control (C), n = 6; maternal obesity (MO), n = 5.
Lomas-Soria C, Reyes-Castro LA, Rodríguez-González GL, Ibáñez CA, Bautista CJ, Cox LA, Nathanielsz PW, Zambrano E. Maternal obesity has sex dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring. J Physiol (Lond). 2018; In Press. PMID: 29972240