Body Adiposity and Endocrine Profile of Female Wistar Rats of
                    Distinct Ages that were Early Weaned

Pietrobon, Carla Bruna; Bertasso, Iala Milene; Silva, Beatrix S.; Peixoto-Silva, Nayara; Oliveira, Elaine de; Moura, Egberto Gaspar de; Lisboa, Patrícia Cristina

doi:10.1055/a-0966-8784

Cited by 11 publications

(16 citation statements)

References 60 publications

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“…Recently, our group demonstrated that PEW females have reduced serum oestrogen levels in adulthood (Pietrobon & Bertasso et al . ), which could contribute to the reduction in insulin secretion in this group, despite the lack of alterations in ERα expression in islets. Epidemiological and experimental studies suggest that oestradiol protects insulin production in diabetic females (Louet et al .…”

Section: Discussionmentioning

confidence: 83%

“…Islets were isolated from fasted offspring at PN45 and PN180 by collagenase (0.8 mg/mL; Sigma‐Aldrich, St Louis, MO, USA, 5% bovine serum albumin (BSA) and 0.6% HEPES according to a previous report (Pietrobon et al . ). After digestion of the exocrine pancreas, the islets were collected with a micropipette under a microscope to exclude any contaminating tissues.…”

Section: Methodsmentioning

confidence: 97%

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Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

Pietrobon

Miranda

Bertasso

et al. 2020

The Journal of Physiology

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Key points The World Health Organization recommends exclusive breastfeeding until 6 months of age as an important strategy to reduce child morbidity and mortality. Studies have associated early weaning with the development of obesity and type 2 diabetes in adulthood. In our model, we demonstrated that early weaning leads to increased insulin secretion in adolescent males and reduced insulin secretion in adult offspring. Early weaned males exhibit insulin resistance in skeletal muscle. Early weaning did not change insulin signalling in the muscle of female offspring. Taking into account that insulin resistance is one of the primary factors for the development of type 2 diabetes mellitus, this work demonstrates the importance of breastfeeding in the fight against this disease. Abstract Early weaning (EW) leads to short‐ and long‐term obesity and diabetes. This phenotype is also observed in experimental models, in which early‐weaned males exhibit abnormal insulinaemia in adulthood. However, studies regarding the effect of EW on pancreatic islets are rare. We investigated the mechanisms by which glycaemic homeostasis is altered in EW models through evaluations of insulin secretion and its signalling pathway in offspring. Lactating Wistar rats and their pups were divided into the following groups: non‐pharmacological EW (NPEW): mothers were wrapped with an adhesive bandage on the last 3 days of lactation; pharmacological EW (PEW): mothers received bromocriptine to inhibit prolactin (1 mg/kg body mass/day) on the last 3 days of lactation; and control (C): pups underwent standard weaning at PN21. Offspring of both sexes were euthanized at PN45 and PN180. At PN45, EW males showed higher insulin secretion (vs. C). At PN170, PEW males exhibited hyperglycaemia in an oral glucose tolerance test (vs. C and NPEW). At PN180, EW male offspring were heavier; however, both sexes showed higher visceral fat. Insulin secretion was lower in EW offspring of both sexes. Males from both EW groups had lower glucokinase in islets, but unexpectedly, PEW males showed higher GLUT2, than did C. EW males exhibited lower insulin signalling in muscle. EW females exhibited no changes in these parameters compared with C. We demonstrated distinct alterations in the insulin secretion of EW rats at different ages. Despite the sex dimorphism in insulin secretion in adolescence, both sexes showed impaired insulin secretion in adulthood due to EW.

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Section: Discussionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 97%

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

Pietrobon

Miranda

Bertasso

et al. 2020

The Journal of Physiology

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“…Female offspring in both pharmacological and NPEW models exhibited higher adiposity and hyperphagia, despite having normal body weight. A sexdependent mechanism seems to be involved in this phenotype because the females showed differences in hormonal profiles, 115 BAT thermogenic capacity, 88 fat deposit distribution, and glucocorticoid status. 111…”

Section: Sex-related Differencesmentioning

confidence: 99%

Does early weaning shape future endocrine and metabolic disorders? Lessons from animal models

Souza

Moura

Lisboa

2020

J Dev Orig Health Dis

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Obesity and its complications occur at alarming rates worldwide. Epidemiological data have associated perinatal conditions, such as malnutrition, with the development of some disorders, such as obesity, dyslipidemia, diabetes, and cardiovascular diseases, in childhood and adulthood. Exclusive breastfeeding has been associated with protection against long-term chronic diseases. However, in humans, the interruption of breastfeeding before the recommended period of 6 months is a common practice and can increase the risk of several metabolic disturbances. Nutritional and environmental changes within a critical window of development, such as pregnancy and breastfeeding, can induce permanent changes in metabolism through epigenetic mechanisms, leading to diseases later in life via a phenomenon known as programming or developmental plasticity. However, little is known regarding the underlying mechanisms by which precocious weaning can result in adipose tissue dysfunction and endocrine profile alterations. Here, the authors give a comprehensive report of the different animal models of early weaning and programming that can result in the development of metabolic syndrome. In rats, for example, pharmacological and nonpharmacological early weaning models are associated with the development of overweight and visceral fat accumulation, leptin and insulin resistance, and neuroendocrine and hepatic changes in adult progeny. Sex-related differences seem to influence this phenotype. Therefore, precocious weaning seems to be obesogenic for offspring. A better understanding of this condition seems essential to reducing the risk for diseases. Additionally, this knowledge can generate new insights into therapeutic strategies for obesity management, improving health outcomes.

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“…Hyperphagia, higher body mass, and TG/leptin serum levels as well as leptin resistance outcomes were also observed in previous studies encompassing other animal models of early weaning. 10,11,29,41,42 Early-weaned rats presented higher LVM, IVS thickness and LVPW thickness, both in diastole, compared to respective adult and elderly controls. RWT was higher in this group at postnatal day 90 but not 150 or 365.…”

Section: Discussionmentioning

confidence: 92%

Biometric, nutritional, biochemical, and cardiovascular outcomes in male rats submitted to an experimental model of early weaning that mimics mother abandoning

Barros

Alvim-Silva

Souza

et al. 2020

J Dev Orig Health Dis

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Literature describes breast milk as the best food for the newborn, recommending exclusive breastfeeding for up to 6 months of age. However, it is not available for more than 40% of children worldwide. Pharmacological and non-pharmacological models of 3-day early weaning were developed in rodents to investigate later outcomes related solely to this nutritional insult. Thus, the present work aimed to describe biometric, nutritional, biochemical, and cardiovascular outcomes in adult male rats submitted to 3-day early weaning achieved by maternal deprivation. This experimental model comprises not only nutritional insult but also emotional stress, simulating mother abandoning. Male offspring were physically separated from their mothers at 21st (control) or 18th (early weaning) postnatal day, receiving water/food ad libitum. Analysis performed at postnatal days 30, 90, 150, and 365 encompassed body mass and food intake monitoring and serum biochemistry determination. Further assessments included hemodynamic, echocardiographic, and cardiorespiratory evaluation. Early-weaned males presented higher body weight when compared to control as well as dyslipidemia, higher blood pressure, diastolic dysfunction, and cardiac hypertrophy in adult life. Animals early deprived of their mothers have also presented a worse performance on the maximal effort ergometer test. This work shows that 3-day early maternal deprivation favors the development of cardiovascular disease in male rats.

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Body Adiposity and Endocrine Profile of Female Wistar Rats of Distinct Ages that were Early Weaned

Cited by 11 publications

References 60 publications

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

Does early weaning shape future endocrine and metabolic disorders? Lessons from animal models

Biometric, nutritional, biochemical, and cardiovascular outcomes in male rats submitted to an experimental model of early weaning that mimics mother abandoning

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