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


METHODS
Female 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.


RESULTS
Offspring subjected to an adverse suckling environment showed significant increases in body weight, pancreatic triglyceride content, TGF-beta, collagen gene expression and SBP at rest along with an enhanced restraint stress response, indicating a dysmetabolic and NAFPD phenotype.


CONCLUSIONS
Developmental programming is involved in the pathogenesis of NAFPD and appears to be largely dependent on an adverse extra-uterine environment.
Oben
Jude A
JA
Centre for Hepatology, University College London, Royal Free Hospital, London NW3 2PF, UK. j.oben@ucl.ac.uk
Patel
Trusha
T
Mouralidarane
Angelina
A
Samuelsson
Ann Maj
AM
Matthews
Phillippa
P
Pombo
Joaquim
J
Morgan
Maelle
M
McKee
Chad
C
Soeda
Junpei
J
Novelli
Marco
M
Poston
Lucilla
L
Taylor
Paul
P
D000818:Animals; D000833:Animals, Suckling; D001794:Blood Pressure; D001835:Body Weight; D024042:Collagen Type I / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D010182:Pancreatic Diseases / Q000209:etiology* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D024042:Collagen Type I; D005227:Fatty Acids; D016212:Transforming Growth Factor beta