Pregestational maternal obesity impairs endocrine pancreas in male F1 and F2 progeny

Graus-Nunes, Francielle; Frantz, Eliete Dalla Corte; Lannes, Wilian Rodrigues; Menezes, Mariel Caroline da Silva; Mandarim-de-Lacerda, Carlos Alberto; Souza-Mello, Vanessa

doi:10.1016/j.nut.2014.08.002

Cited by 43 publications

(33 citation statements)

References 42 publications

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“…Another study of chronic administration a HF diet both before and during pregnancy resulted in decreased fetal birth weight in rodents, which suggests some degree of placental insufficiency (Howie et al). The present findings are in agreement with previous results of our laboratory as offspring from HF-fed mothers were smaller at birth but has a catch-up growth, showing overweight at weaning (Gregorio et al;Bringhenti et al;Graus-Nunes et al, 2015).…”

Section: Discussionsupporting

confidence: 94%

Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

et al. 2015

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SUMMARY:The high fat (HF) fed mothers may program susceptibility in offspring to chronic diseases and affect subsequent generations. The present study evaluated the liver structure in adulthood, focusing on the F1 and F2 generations. Females C57BL/6 (F0) were fed standard chow (SC) or HF diet (8 weeks) prior to mating and during the gestation and lactation to provide the F1 generation (SC-F1 and HF-F1). All other mothers and offspring fed SC. At 3 months old, F1 females were mated to produce the F2 generation (SC-F2 and HF-F2). The liver was kept in several fragments and prepared for histological analysis or frozen for biochemical and molecular analyzes. The F1 and F2 offspring were studied at 3 months old. HF-F1 had higher body mass (BM) compared to SC-F1 (P= 0.001), but not HF-F2 compared to SC-F2. HF-F1 had glucose intolerance when compared to SC-F1, but not HF-F2 compared to SC-F2. HF-F1 (P= 0.009) and HF-F2 (P= 0.03) showed hyperinsulinemia compared to their counterparts. Both groups HF-F1 and HF-F2 showed more steatosis than the SC counterparts (F1 and F2, P<0.0001). HF-F1 showed increased expression of PPAR-gamma and SREBP1-c compared to SC-F1 (P= 0.01). HF-F2 showed increased PPAR-gamma expression compared to SC-F2 (P= 0.04). In conclusion, HF-fed mother impairs both lipogenesis and beta-oxidation pathways in F1 through upregulation of PPAR-gamma and downregulation of PPAR-alpha. In F2, the only lipogenesis is enhanced, but it causes a disrupted PPAR balance, favoring the hepatic lipid accumulation and impaired metabolism in these animals that were not directly exposed to the maternal HF intake.

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Section: Discussionsupporting

confidence: 94%

Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

et al. 2015

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“…Germination reduces the build-up of fatty acids (observed lipid profile reduction) from de novo lipogenesis - which impairs insulin signalling partly through inflammatory processes [28] - and this is partly responsible for its retardant effect on IR. Pups inherited markers of dyslipidaemia (high TG, LDL and TC levels), obesity (apparent leptin and adiponectin levels) and IR, although these effects were not associated with increased body weight or changes in AUC values and this provides evidence that pregestational maternal metabolic disorders affect progeny [29]. The inherited effects of pregestational maternal diet were especially pronounced in the pups of dams fed with LAWR in the context of a HFD.…”

Section: Discussionmentioning

confidence: 99%

Predisposition to insulin resistance and obesity due to staple consumption of rice: Amylose content versus germination status

et al. 2017

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Type 2 diabetes is a metabolic disorder with established, well-defined precursors. Obesity and insulin resistance are amongst most important factors in predisposition to diabetes. Rice is a staple for about half the global population and its consumption has been strongly linked with diabetogenesis. We assert that tackling the prevalence of predisposing factors by modifying certain rice cultivars could reduce the global burden of obesity and insulin resistance, and by extension type 2 diabetes. Several rice cultivars with various properties were fed to nulliparous rats (five weeks old at the start of the experiment) for 90 days. They were then returned to a diet of standard pellets and mated with males raised on a standard diet. The resulting pups and dams were investigated for obesity and insulin resistance markers. We found that germination did more to reduce predisposition to obesity and insulin resistance than high amylose content. The combined reducing effect of germination and high amylose content on predisposition to obesity and insulin resistance was greater than the sum of their independent effects. Polished (white) rice with a low amylose content predisposed dams on a high-fat diet to markers of insulin resistance and obesity and this predisposition was inherited (in biochemical terms) by their F1 offspring. Overall, the results suggest that harnessing the beneficial properties of germination and amylose in rice would reduce the burden of obesity and insulin resistance, which are known to be key risk factors for development of type 2 diabetes.

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“…A number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function (reviewed in [5]). Whilst findings of reduced beta cell mass and impaired glucose-stimulated insulin secretion (GSIS) suggest increased type 2 diabetes susceptibility, most previous studies have not delineated whether these changes in islet structure/function are independent of other confounding risk factors such as obesity/increased body weight in the offspring [6][7][8][9], postnatal high-fat-feeding [9,10] and the effects of ageing [8,10]. Importantly, research by Zambrano et al in 5-week-old rat offspring exposed to maternal obesity suggested that islet function may already be impacted in young life [11].…”

Section: Introductionmentioning

confidence: 99%

Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice

et al. 2019

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Aims/hypothesis Obesity during pregnancy increases offspring type 2 diabetes risk. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Whilst a number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function, it has not previously been delineated whether these changes are independent of other confounding risk factors such as obesity, postnatal highfat-feeding and ageing. Thus, we aimed to study the impact of exposure to maternal obesity on offspring islets in young, glucose-tolerant male and female offspring. Methods Female C57BL/6J mice were fed ad libitum either chow or obesogenic diet prior to and throughout pregnancy and lactation. Offspring were weaned onto a chow diet and remained on this diet until the end of the study. An IPGTT was performed on male and female offspring at 7 weeks of age. At 8 weeks of age, pancreatic islets were isolated from offspring for measurement of insulin secretion and content, mitochondrial respiration, ATP content, reactive oxygen species levels, beta and alpha cell mass, granule and mitochondrial density (by transmission electron microscopy), and mRNA and protein expression by real-time RT-PCR and Western blotting, respectively. Results Glucose tolerance was similar irrespective of maternal diet and offspring sex. However, blood glucose was lower (p < 0.001) and plasma insulin higher (p < 0.05) in female offspring of obese dams 15 min after glucose administration. This was associated with higher glucose-(p < 0.01) and leucine/glutamine-stimulated (p < 0.05) insulin secretion in these offspring. Furthermore, there was increased mitochondrial respiration (p < 0.01) and density (p < 0.05) in female offspring of obese dams compared with same-sex controls. Expression of mitochondrial and nuclear-encoded components of the electron transport chain, L-type Ca 2+ channel subtypes that play a key role in stimulus-secretion coupling [Cacna1d (p < 0.05)], and oestrogen receptor α (p < 0.05) was also increased in islets from these female offspring of obese dams. Moreover, cleaved caspase-3 expression and BAX:Bcl-2 were decreased (p < 0.05) reflecting reduced susceptibility to apoptosis. In contrast, in male offspring, glucose and leucine/glutamine-stimulated insulin secretion was comparable between treatment groups. There was, however, compromised mitochondrial respiration characterised by decreased ATP synthesis-driven respiration (p < 0.05) and increased uncoupled respiration (p < 0.01), reduced docked insulin granules (p < 0.001), decreased Cacna1c (p < 0.001) and Cacna1d (p < 0.001) and increased cleaved caspase-3 expression (p < 0.05).

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Pregestational maternal obesity impairs endocrine pancreas in male F1 and F2 progeny

Cited by 43 publications

References 42 publications

Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

Predisposition to insulin resistance and obesity due to staple consumption of rice: Amylose content versus germination status

Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice

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