Epigenetic and Molecular Mechanisms of Prenatal Programming of Diabetes with Obesity

Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Sofia

 

Abstract:

Various factors play role in the mechanisms that underlie the development of type 2 diabetes mellitus (T2DM). It is well known that obesity is one of them. The prenatal programming of T2DM with or without obesity is an important factor.

Some epigenetic as well as molecular mechanisms in prenatal programming of T2DM are illustrated in the present review. It is well known that the adipocytes have a capacity to produce and secrete approximately 50 substances (named adipocytokines –peptides, cytokines, etc.) and part of them play a role in the intrauterine determination of the T2DM risk. Various cytokines as TNF alpha, IL-6 and IL-1 are well recognized in the fetal programming of obesity and T2DM. In addition, genetic studies have documented the role of gene mutations for the early programming of diabetes. Recent data from experimental studies in mice indicated the role of the Klotho gene and the capacity of high fat food to activate it in prenatal programming of metabolic diseases. Various substances produced from the adipocytes like the ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular adhesion molecule-1) and hs CRP (C-reactive protein) are recognized to participate in the intrauterine programming of T2DM. Epigenetic modifications like histone methylation, histone acetylation and DNA methylation are involved in the prenatal pathogenesis of obesity and T2DM. Together these data suggest that adipocytokines and epigenetic modifications are involved in the mechanisms of prenatal programming of the metabolic diseases.

 

Keywords: type 2 diabetes mellitus, epigenetics, adipocytokines, interleukins, obesity