Maternal obesity programmes offspring development of non-alcoholic fatty pancreas disease

Abstract

Background and aimsThe prevalence of pancreatic adenocarcinoma (PAC) parallels rising rates of obesity and dysmetabolism, a possible link being non-alcoholic fatty pancreas disease (NAFPD). We have recently shown that maternal obesity programmes the development of a dysmetabolic and fatty liver (non-alcoholic fatty liver disease, NAFLD) phenotype in adult offspring. Since the pancreas and liver originate from the same embryonic bud, it is plausible that maternal obesity may similarly programme the development of NAFPD. Our objective was to determine the effect of maternal obesity on development of NAFPD in offspring and ascertain contributions of the intra/extra-uterine periods.MethodsFemale C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a hypercalorific diet (16% fat, 33% sugar) for six weeks prior to mating and throughout pregnancy and lactation. Female offspring were cross-fostered for suckling to dams on the same or opposite diet to yield four groups: offspring of lean suckled by lean dams (n = 6), offspring of obese suckled by obese dams (n = 6), offspring of lean suckled by obese dams (n = 5) and offspring of obese suckled by lean dams (n = 6). All offspring were weaned onto a standard chow diet at 21 days and sacrificed at 3 months post-partum for tissue collection.ResultsOffspring subjected to an adverse suckling environment showed significant increases in body weight, pancreatic triglyceride content, TGF-β, collagen gene expression and SBP at rest along with an enhanced restraint stress response, indicating a dysmetabolic and NAFPD phenotype.ConclusionsDevelopmental programming is involved in the pathogenesis of NAFPD and appears to be largely dependent on an adverse extra-uterine environment.

Non-Alcoholic Fatty Pancreas Disease Pathogenesis: A Role for Developmental Programming and Altered Circadian Rhythms

“…Here, we corroborate these results using a more pathophysiologically relevant model not involving cross-fostering which has since been shown to influence metabolic phenotype [35]. In addition to the previous findings of increased pancreatic triglycerides, collagen and TGF-β expression [1], our results show that MO in conjunction with a post-weaning OD (Ob_Ob) significantly impacts upon pancreas weight, pancreatic triglycerides concentration and macrovesicular fat concentration.…”

“…The similarity in phenotypes could be due to the common embryonic origins of the liver and pancreas. We have previously shown that offspring exposure to MO throughout pregnancy and lactation induces a significant increase in markers indicative of a NAFPD phenotype, when compared to offspring exposed to a normal intrauterine and perinatal environment [1]. Here, we corroborate these results using a more pathophysiologically relevant model not involving cross-fostering which has since been shown to influence metabolic phenotype [35].…”

“…We have previously shown, in a rodent model, that diet induced maternal obesity can play a causative role in the development of NAFPD and that this is exacerbated if the offspring themselves are reared on the same obesogenic diet [1].…”

Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature

“…These dysmetabolic offspring had a significant increase in body weight, pancreas tissue triglyceride content, increased pancreatic expression of the fibrogenic markers TGF-β1 and collagen gene along with increases in a hypertensive phenotype [16]. …”

Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

“…[33][34][35] This has been associated with altered expression of key components of the insulin-signaling pathway including insulin receptor substrate 1. 30,[37][38][39] The subsequent development of obesity could further increase the development of insulin resistance. It should be noted that the results above are more commonly reported in male offspring although many studies observe comparative affects in female littermates.…”