Maternal Obesity during the Preconception and Early Life Periods Alters Pancreatic Development in Early and Adult Life in Male Mouse Offspring

Abstract

Maternal obesity induced by a high fat (HF) diet may program susceptibility in offspring, altering pancreatic development and causing later development of chronic degenerative diseases, such as obesity and diabetes. Female mice were fed standard chow (SC) or an HF diet for 8 weeks prior to mating and during the gestational and lactational periods. The male offspring were assessed at birth, at 10 days, and at 3 months of age. The body mass (BM) gain was 50% greater before pregnancy and 80% greater during pregnancy in HF dams than SC dams. Dams fed an HF diet showed higher oral glucose tolerance test (OGTT), blood pressure, serum corticosterone, and insulin levels than dams fed SC. At 10 days of age and at 3 mo old the HF offspring showed greater BM and higher blood glucose levels than the SC offspring. The mean diameter of the islets had increased by 37% in the SC offspring and by 155% in the HF offspring at 10 days of age. The islet mass ratio (IM/PM) was 88% greater in the HF offspring at 10 days of age, and 107% greater at 3 mo of age, compared to the values obtained at birth. The HF offspring had a beta cell mass (BCM)/PM ratio 54% lower than SC offspring at birth. However, HF offspring displayed a 146% increase in the BCM/PM ratio at 10 days of age, and 112% increase at 3 months of age than values at birth. A 3 mo of age, the HF offspring showed a greater OGTT and higher levels of than SC offspring. In conclusion, a maternal HF diet consumed during the preconceptional period and throughout the gestational and lactational periods in mice results in dramatic alterations in the pancreata of the offspring.

High fat programming of beta cell compensation, exhaustion, death and dysfunction

“…In reference to these studies, mice maintained on a HFD throughout preconception, gestation, and lactation showed pancreas remodeling and beta cell hypertrophy that restored beta cell mass at the end of organogenesis (14). Maintenance or altering the diet after weaning and particularly HFDs during pregnancy structurally altered beta cells in progeny (15).…”

Developmental overnutrition and obesity and type 2 diabetes in offspring

“…The intrauterine effect of maternal obesity on offspring obesity is difficult to isolate in human studies, but animal experiments support biological plausibility. Diet-induced obesity among pregnant rodents altered offspring adipocyte metabolism to favour hypertrophy via epigenetic modifications [71][72][73][74]. Other pathways include the effect of maternal obesity on placental function [75], glycaemic regulation [76] and stem cell differentiation [77][78][79][80][81].…”

Development of a Computational High-Throughput Tool for the Quantitative Examination of Dose-Dependent Histological Features

“…Manual point counting and computational feature extraction have been used to analyze digital images. Morphometry is commonly used for quantitation of histological features (Bringhenti et al 2013; Frantz et al 2013) aided by programs such as STEPanizer and Image-Pro Plus (Tschanz et al 2011; Bringhenti et al 2013; Frantz et al 2013). Although visual-based assessment is the current standard for quantitation of histological features, it is time consuming, tedious, and vulnerable to inter- and intraobserver variability.…”