Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition
Objective: In humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of mate...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-07-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877819301425 |
| _version_ | 1828436480789315584 |
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| author | Joseph M. Elsakr Jennifer C. Dunn Katherine Tennant Sifang Kathy Zhao Karly Kroeten Raymond C. Pasek Diana L. Takahashi Tyler A. Dean Digna R. Velez Edwards Carrie E. McCurdy Kjersti M. Aagaard Alvin C. Powers Jacob E. Friedman Paul Kievit Maureen Gannon |
| author_facet | Joseph M. Elsakr Jennifer C. Dunn Katherine Tennant Sifang Kathy Zhao Karly Kroeten Raymond C. Pasek Diana L. Takahashi Tyler A. Dean Digna R. Velez Edwards Carrie E. McCurdy Kjersti M. Aagaard Alvin C. Powers Jacob E. Friedman Paul Kievit Maureen Gannon |
| author_sort | Joseph M. Elsakr |
| collection | DOAJ |
| description | Objective: In humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of maternal diet on the structure and function of offspring islets with characteristics similar to humans are unknown. We used a well-established non-human primate (NHP) model to determine the consequences of exposure to Western-Style Diet (WSD) in utero and during lactation on islet cell mass and function in the offspring. Methods: Female Japanese Macaques (Macaca fuscata) were fed either control (CTR) or WSD before and throughout pregnancy and lactation. Offspring were weaned onto CTR or WSD to generate four different groups based on maternal/offspring diets: CTR/CTR, WSD/CTR, CTR/WSD, and WSD/WSD. Offspring were analyzed at three years of age. Pancreatic tissue sections were immunolabelled to measure α- and β-cell mass and proliferation as well as islet vascularization. Live islets were also isolated to test the effects of WSD-exposure on islet function ex vivo. Offspring glucose tolerance was correlated with various maternal characteristics. Results: α-cell mass was reduced as a result of maternal WSD exposure. α-cell proliferation was reduced in response to offspring WSD. Islet vasculature did not differ among the diet groups. Islets from WSD/CTR offspring secreted a greater amount of insulin in response to glucose ex vivo. We also found that maternal glucose tolerance and parity correlated with offspring glucose tolerance. Conclusions: Maternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions. Keywords: Developmental origins, Diabetes, Beta cell, Alpha cell, Fetal programming |
| first_indexed | 2024-12-10T19:28:07Z |
| format | Article |
| id | doaj.art-59c889a547274a3b82f1ccc31a532c7e |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-10T19:28:07Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-59c889a547274a3b82f1ccc31a532c7e2022-12-22T01:36:19ZengElsevierMolecular Metabolism2212-87782019-07-01257382Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutritionJoseph M. Elsakr0Jennifer C. Dunn1Katherine Tennant2Sifang Kathy Zhao3Karly Kroeten4Raymond C. Pasek5Diana L. Takahashi6Tyler A. Dean7Digna R. Velez Edwards8Carrie E. McCurdy9Kjersti M. Aagaard10Alvin C. Powers11Jacob E. Friedman12Paul Kievit13Maureen Gannon14Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USADepartment of Veterans Affairs Tennessee Valley, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADivision of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR, USAVanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Summer Diabetes Research Program, Vanderbilt University, Nashville, TN, USADepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADivision of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR, USADivision of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR, USAVanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Informatics, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Human Physiology, University of Oregon, Eugene, OR, 97403, USADepartment of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX, 77030, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs Tennessee Valley, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Pediatrics, Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USADivision of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs Tennessee Valley, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, USA; Corresponding author. Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, 2213 Garland Avenue, 7465 MRBIV, Vanderbilt University Medical Center, Nashville, TN 37232-0475, USA. Fax: +615 936 1667.Objective: In humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of maternal diet on the structure and function of offspring islets with characteristics similar to humans are unknown. We used a well-established non-human primate (NHP) model to determine the consequences of exposure to Western-Style Diet (WSD) in utero and during lactation on islet cell mass and function in the offspring. Methods: Female Japanese Macaques (Macaca fuscata) were fed either control (CTR) or WSD before and throughout pregnancy and lactation. Offspring were weaned onto CTR or WSD to generate four different groups based on maternal/offspring diets: CTR/CTR, WSD/CTR, CTR/WSD, and WSD/WSD. Offspring were analyzed at three years of age. Pancreatic tissue sections were immunolabelled to measure α- and β-cell mass and proliferation as well as islet vascularization. Live islets were also isolated to test the effects of WSD-exposure on islet function ex vivo. Offspring glucose tolerance was correlated with various maternal characteristics. Results: α-cell mass was reduced as a result of maternal WSD exposure. α-cell proliferation was reduced in response to offspring WSD. Islet vasculature did not differ among the diet groups. Islets from WSD/CTR offspring secreted a greater amount of insulin in response to glucose ex vivo. We also found that maternal glucose tolerance and parity correlated with offspring glucose tolerance. Conclusions: Maternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions. Keywords: Developmental origins, Diabetes, Beta cell, Alpha cell, Fetal programminghttp://www.sciencedirect.com/science/article/pii/S2212877819301425 |
| spellingShingle | Joseph M. Elsakr Jennifer C. Dunn Katherine Tennant Sifang Kathy Zhao Karly Kroeten Raymond C. Pasek Diana L. Takahashi Tyler A. Dean Digna R. Velez Edwards Carrie E. McCurdy Kjersti M. Aagaard Alvin C. Powers Jacob E. Friedman Paul Kievit Maureen Gannon Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition Molecular Metabolism |
| title | Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition |
| title_full | Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition |
| title_fullStr | Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition |
| title_full_unstemmed | Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition |
| title_short | Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition |
| title_sort | maternal western style diet affects offspring islet composition and function in a non human primate model of maternal over nutrition |
| url | http://www.sciencedirect.com/science/article/pii/S2212877819301425 |
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