Intergenerational effects of prenatal ethanol on glucose tolerance and insulin response

Abstract

Consequences of prenatal exposure to ethanol (E) include morphological, physiological, and cognitive deficits and are collectively classified as fetal alcohol spectrum disorders. Adult prenatal E exposed offspring show insulin resistance, and given that in utero hyperglycemic environment can cause metabolic disorders in subsequent generations; we investigated the effects of grandmaternal E on functional glucose and insulin responses of the second generation. Sprague-Dawley (S) rat dams, mated with S males, received E-containing liquid diet and two different control diets between gestational days 8 and 20. Additionally, because prenatal E-induced behavioral deficits can be reversed by simultaneous thyroxine (T4) treatment, another group of dams received 0.3 mg/l T4 in their E diet. Their first-generation (F1) offspring were mated with control Brown Norway (B) males or females to produce SB and BS F2 progeny. Dams consuming E during pregnancy were hyperglycemic, and their F1 offspring showed insulin resistance in the glucose tolerance test (GTT). However, F2 responses to GTT varied based on the sex of prenatal E-exposed parent. BS F2 females, and both male and female SB F2 progeny, displayed hypoglycemic and hyperinsulinemic GTT response patterns. Although administering T4 to E dams normalized thyroid function of the F1 generation, it did not reverse their prenatal E-induced metabolic dysfunction. In contrast, administration of T4 to the alcohol-consuming grandmother reversed or alleviated the aberrant GTT responses of the F2 progeny. Prenatal E-induced dysregulation of glucose metabolism can affect the next generation, possibly via ethanol effects on the germline of the F1 fetus.

Prenatal Alcohol Exposure Alters Steady‐State and Activated Gene Expression in the Adult Rat Brain

“…Activation of Laminin could also be involved in the altered neuronal migration patterns observed in PAE brains (Ozer et al, 2000). Moreover, inappropriate feeding behaviour in children with FASD, as well as altered glucose metabolism and insulin tolerance in PAE animals have been reported (Werts et al, 2014; Harper et al 2014). As Rgs3 negatively regulates glucose output via cAMP production in hepatic cells, it may also play a role in altered energy metabolism within the brain when combined with the activation of gastrin and leptin in the PFC (Raab et al, 2005).…”

Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus

“…From GD4-8, CR rats were provided with water and a liquid diet (Lieber-DeCarli ’82; Bio-Serv. Frenchtown, NJ, USA) ad libitum to acclimatize them to the diet as described previously (Harper et al, 2014). From GD8-21, CR rats consumed an average of 21.8 to 26.8 kcal per 100 g −1 of body weight per day.…”

Early-Life Exposure to Substance Abuse and Risk of Type 2 Diabetes in Adulthood

“…Remarkably, the programming effects of alcohol consumption during pregnancy were shown to be able to persist across generations. In the study by Harper et al [48], the effects of grandmaternal exposure to alcohol on insulin and functional glucose responses in the second-generation offspring were observed, possibly owing to the effect of alcohol on the germ line of the F1 fetus.…”