Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalMolecular Metabolism
DOIs
StatePublished - Jan 1 2019

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Primates
Mothers
Diet
Glucose
Macaca
Insulin
Islets of Langerhans
Lactation
Cell Proliferation
Glucose Intolerance
Metabolic Diseases
Glucose Tolerance Test
Parity

Keywords

  • Alpha cell
  • Beta cell
  • Developmental origins
  • Diabetes
  • Fetal programming

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition. / Elsakr, Joseph M.; Dunn, Jennifer C.; Tennant, Katherine; Zhao, Sifang Kathy; Kroeten, Karly; Pasek, Raymond C.; Takahashi, Diana L.; Dean, Tyler A.; Velez Edwards, Digna R.; McCurdy, Carrie E.; Aagaard, Kjersti M.; Powers, Alvin C.; Friedman, Jacob E.; Kievit, Paul; Gannon, Maureen.

In: Molecular Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

Elsakr, JM, Dunn, JC, Tennant, K, Zhao, SK, Kroeten, K, Pasek, RC, Takahashi, DL, Dean, TA, Velez Edwards, DR, McCurdy, CE, Aagaard, KM, Powers, AC, Friedman, JE, Kievit, P & Gannon, M 2019, 'Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition', Molecular Metabolism. https://doi.org/10.1016/j.molmet.2019.03.010
Elsakr, Joseph M. ; Dunn, Jennifer C. ; Tennant, Katherine ; Zhao, Sifang Kathy ; Kroeten, Karly ; Pasek, Raymond C. ; Takahashi, Diana L. ; Dean, Tyler A. ; Velez Edwards, Digna R. ; McCurdy, Carrie E. ; Aagaard, Kjersti M. ; Powers, Alvin C. ; Friedman, Jacob E. ; Kievit, Paul ; Gannon, Maureen. / Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition. In: Molecular Metabolism. 2019.
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abstract = "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.",
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AU - Elsakr, Joseph M.

AU - Dunn, Jennifer C.

AU - Tennant, Katherine

AU - Zhao, Sifang Kathy

AU - Kroeten, Karly

AU - Pasek, Raymond C.

AU - Takahashi, Diana L.

AU - Dean, Tyler A.

AU - Velez Edwards, Digna R.

AU - McCurdy, Carrie E.

AU - Aagaard, Kjersti M.

AU - Powers, Alvin C.

AU - Friedman, Jacob E.

AU - Kievit, Paul

AU - Gannon, Maureen

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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KW - Beta cell

KW - Developmental origins

KW - Diabetes

KW - Fetal programming

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