Intrauterine diabetic milieu instigates dysregulated adipocytokines production in F1 offspring
There is a compelling clinical and epidemiological evidence suggests that prenatal environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome and its components: hypertension, insulin resistance, and dyslipidemia [1]. The altered maternal metabolism in diabetic mothers appears to be associated with a diabetogenic effect in the adult offspring, through adaptations during intrauterine fetal development [2]. This intrauterine programming could occur at the gene, cellular, tissue, organ, and system levels, culminating in long-lasting structural and functional changes [3].
Adiponectin have insulin-sensitizing, anti-diabetic, antioxidant, anti-inflammatory and anti-atherogenic properties through its action on adiponectin receptors, e.g., AdipoR1 and AdipoR2 [4]. Leptin is an adipokines involved in the pathogenesis of obesity, insulin resistance, inflammation, and diabetes. It has a regulatory action on satiety and energy homeostasis, production of inflammatory mediators, and on lipid and carbohydrate metabolism [4]. Diabetes is associated with decreased levels of adiponectin and increased levels of leptin. This reflects a state of adiponectin deficiency and leptin resistance, which could be a possible mechanism for development of diabetes complications [4–6].
Low-grade inflammation is a hallmark of type 2 diabetes and metabolic syndrome [4]. Tumor necrosis factor-? (TNF-?) is an inflammatory cytokine that has a myriad of functions such as mediating apoptosis and regulation of immune system. TNF-? exerts its effects among various cells via its action on its TNFR1 and TNFR2 receptors [4]. Serum TNF-? level is elevated in type 1 and type 2 diabetic patients and is correlated with various complications of diabetes [7, 8].
Intrauterine epigenetic modifications, deterioration of glucose tolerance and oxidative stress could be a possible mechanisms for the transgenerational transmittance of diabetes [9, 10]; however, the exact mechanism is not fully understood. Therefore, the aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-?) production in F1 offspring in rats, as a potential mechanism for the transgenerational effect of maternal diabetes.