Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy
Taylor, P.D., McConnell, J., Khan, I.Y., Holemans, K., Lawrence, K.M., Sare-Anane, H., Persaud, S.J., Jones, P.M., Petrie, L., Hanson, M.A. and Poston, L. (2005) Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. American Journal of Physiology.Regulatory, Integrative and Comparative Physiology, 288, (1), R134-R139. (doi:10.1152/ajpregu.00355.2004).
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We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dyslipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague-Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU·kg–1·min–1) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC (n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic -cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC (n = 10) 1.05 ± 0.19 vs. OHF (n = 10) 0.66 ± 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic -cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.
|Keywords:||dietary fats, insulin, islet cells, metabolic syndrome|
|Subjects:||R Medicine > RG Gynecology and obstetrics
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
|Date Deposited:||20 Apr 2006|
|Last Modified:||01 Apr 2012 02:28|
|Contact Email Address:||M.Hanson@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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