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Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy
Abstract
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 β-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 β-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.
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“Several of these studies have reported hyperlipidemia [96,100], including elevated free fatty acids, plasma triacylglycerol and reduced total and HDL cholesterol in the offspring, though one study did not observe alterations in plasma lipids [101].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [101]
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Metadata
- Authors
- Taylor, P. D., McConnell, J., Khan, I. Y., Holemans, K., Lawrence, K. M., Asare-Anane, H., Persaud, S. J., Jones, P. M., Petrie, L., Hanson, M. A., & Poston, L.
- Affiliations
- King's College London (GB)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2005-01
- Volume
- 288
- Issue
- 1
- Pages
- R134-R139
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2135070381
- Cited by
- 297
- References
- 37
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 14 · 2018: 13 · 2017: 13 · 2016: 20 · 2015: 11 · 2014: 29 · 2013: 14 · 2012: 18
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- maternal high-fat diet, prenatal exposure, offspring, glucose homeostasis, insulin resistance, glucose-stimulated insulin secretion, beta-cell dysfunction, insulin secretory granules, mitochondrial DNA, mitochondrial gene expression, kidney mitochondria, aorta, type 2 diabetes, dyslipidemia, hyperglycemia, cardiovascular dysfunction
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Weight, Dietary Fats, Female, Homeostasis, Insulin, Insulin Resistance, Islets of Langerhans, Lipids, Mitochondria, Pregnancy, Prenatal Exposure Delayed Effects, Gene Expression, Rats, Sprague-Dawley, Leptin, Metabolic Syndrome, Prenatal Nutritional Physiological Phenomena, Rats
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