Why and How Imprinted Genes Drive Fetal Programming

Abstract

Imprinted genes mediate fetal and childhood growth and development, and early growth patterns drive fetal programming effects. However, predictions and evidence from the kinship theory of imprinting have yet to be directly integrated with data on fetal programming and risks of metabolic disease. I first define paternal-gene and maternal-gene optima with regard to early human growth and development. Next, I review salient evidence with regard to imprinted gene effects on birth weight, body composition, trajectories of feeding and growth, and timing of developmental stages, to evaluate why and how imprinted gene expression influences risks of metabolic disease in later life. I find that metabolic disease risks derive primarily from maternal gene biases that lead to reduced placental efficacy, low birth weight, low relative muscle mass, high relative white fat, increased abdominal adiposity, reduced pancreatic β-cell mass that promotes insulin resistance, reduced appetite and infant sucking efficacy, catch-up fat deposition from family foods after weaning, and early puberty. Paternal gene biases, by contrast, may contribute to metabolic disease via lower rates of brown fat thermiogenesis, and through favoring more rapid postnatal catch-up growth after intrauterine growth restriction from environmental causes. These disease risks can be alleviated through dietary and pharmacological alterations that selectively target imprinted gene expression and relevant metabolic pathways. The kinship theory of imprinting, and mother-offspring conflict more generally, provide a clear predictive framework for guiding future research on fetal programming and metabolic disease.

Metabolic Heat in Microbial Conflict and Cooperation

“…Familial conflicts over physiological traits often associate with genomic imprinting in mammals 16 . Several imprinted genes in mice and humans influence thermogenesis and follow the common pattern for familial conflict 14,17 .…”

Obesity and Related Type 2 Diabetes: A Failure of the Autonomic Nervous System Controlling Gastrointestinal Function?

“…Epigenetics can be defined as molecular mechanisms that establish and maintain mitotically stable variations of gene expression involving DNA methylation and histone methylation without altering the genetic sequence [13,14]. These epigenetic marks are established in the parent's germ line (sperm or egg cells) (genetic imprinting) and are maintained through mitotic cell divisions in the somatic cells of an organism [15].…”

Metabolic Heat in Microbial Conflict and Cooperation

“…Familial conflicts over physiological traits often associate with genomic imprinting in mammals 17 . Several imprinted genes in mice and humans influence thermogenesis and follow the common pattern for familial conflict 15,18 .…”