Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring.
OBJECTIVE
Obesity is a global problem with high risks of cardiovascular diseases, stroke and type 2 diabetes. It is well known that maternal obesity affects offspring by inducing malformation, functional abnormalities in many organs and cells, and by increased risk of obesity and type 2 diabetes. However, little is known about abnormalities induced by maternal obesity in pancreatic beta cells of offspring.


METHODS
We used mouse mothers with the Agouti yellow modification on a C57BL/6 background as a maternal model of normoglycaemic obesity, and produced Agouti-negative offspring. Half of the offspring were fed a high-fat diet. Offspring glucose tolerance was tested at different ages, and animals were killed at 50 weeks of age for islet function analysis.


RESULTS
Maternal obesity impaired glucose tolerance in female offspring fed a high-fat diet, and significantly reduced insulin secretion at 50 weeks of age in female offspring that had been fed a normal diet and high-fat diet. Insulin secretion and glucose potentiation from these islets were significantly reduced. Islet protein, DNA and insulin contents were increased while glyceraldehyde-3-phosphate dehydrogenase and transketolase activities were reduced in female offspring.


CONCLUSIONS
Our results indicate that maternal obesity has a long-term effect on the beta cells of female, but not of male, offspring, and leads to increased risk of gestational diabetes and type 2 diabetes in the offspring's later lives.
Han
J
J
The Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 570 South Preston Street, Suite 304, Louisville, KY 40202, USA.
Xu
J
J
Epstein
P N
PN
Liu
Y Qi
YQ
D000064:Acclimatization; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D018445:Infectious Disease Transmission, Vertical; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D025221:Phosphofructokinases / Q000378:metabolism; D011247:Pregnancy; D014174:Transketolase / Q000378:metabolism
D001786:Blood Glucose; D004041:Dietary Fats; D014174:Transketolase; D025221:Phosphofructokinases; D005947:Glucose