Maternal overnutrition during pregnancy: impacts on pancreatic proteome of the offspring

Abstract

Maternal obesity, resulting from high caloric intake during pregnancy, can impair pancreatic development in the offspring and lead to an increased risk of diabetes. We hypothesized that maternal obesity during pregnancy results in reduced expression of proteins associated with pancreatic β cell function and increased expression of proteins associated with apoptosis. C57BL/6J ( N = 6) female mice were fed either a control (CON; n = 3) or a high-fat (HFD; n = 3) diet for fourteen weeks prior to pregnancy, diets were continued throughout gestation and lactation. Offspring were weaned at four weeks and then maintained on a control diet. At eight weeks of age, the offspring were euthanized ( N = 20; 4–6/treatment/sex) and pancreas tissue samples were collected. Protein was isolated and analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry. A total of 2,329 proteins were identified across both male and female mice in the comparison between the control and HFD groups, with 165 differentially expressed (DE) proteins (CON vs HFD males: 145; CON vs HFD females: 20; P ≤ 0.05). In male offspring, 131 DE proteins were down regulated, and 14 were upregulated, while in females 13 were upregulated and seven were down regulated. Four DE proteins (Mgat2, Lama2, Isyna1, Got2) were common to both sexes. However, only Lama2 exhibited a similar pattern of expression, with both HFD males and females having greater expression than CON. Alternatively, HFD males exhibited reduced expression of Mgat2, Got2, and Isyna1 when compared with CON. HFD females exhibited increased gene expression for the DEPs.