Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity

Glastras, Sarah J.; Chen, Hui; McGrath, Rachel T.; Zaky, Amgad; Gill, Anthony J.; Pollock, Carol; Saad, Sonia

doi:10.1038/srep23525

Cited by 44 publications

(61 citation statements)

References 34 publications

(39 reference statements)

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“…Studies, including our own, have shown that the offspring of obese mothers are significantly predisposed to obesity (20,(25)(26)(27)(28). In our previous studies in rodents, maternal obesity increased fat mass in the offspring, and this effect was further amplified when the offspring consumed a high-fat diet after weaning (20,28). Additionally, maternal obesity increases the offspring's risk of dysglycemia, diabetes, and hypertension, which may propagate renal dysfunction in later life (4).…”

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 80%

“…Maternal obesity also plays a significant role in the fetal programming of several adult chronic diseases. Studies, including our own, have shown that the offspring of obese mothers are significantly predisposed to obesity (20,(25)(26)(27)(28). In our previous studies in rodents, maternal obesity increased fat mass in the offspring, and this effect was further amplified when the offspring consumed a high-fat diet after weaning (20,28).…”

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 81%

“…New evidence suggests that maternal obesity may increase the risk of CKD for the offspring via maternal-fetal transmission. Because the estimated prevalence of obesity in women of reproductive age in the United States is 31.8%, and rates are similar in other developed countries, including the United Kingdom and Australia (19), maternal obesity may set forth the above-described pathophysiologic mechanisms from early in prenatal life (20). This concept that adverse conditions during early life increase the susceptibility to chronic diseases in adulthood underpins the theory of the developmental origins of health and disease (21).…”

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 99%

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DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

et al. 2018

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Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

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Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 80%

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 81%

Section: Fetal Programming Maternal Transmission Of Disease and Epimentioning

confidence: 99%

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DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

et al. 2018

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“…Indeed, we have previously shown that inflammatory cytokines including IL-6, MCP-1 and TGFβ are increased in the serum of rat offspring of obese mothers, as well as in their kidneys1433. Thus, exposure to maternal obesity may prime offspring towards a pro-inflammatory state, thereby increasing their susceptibility to complications of obesity and kidney disease at a later stage.…”

Section: Discussionmentioning

confidence: 98%

Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring

Glastras

Tsang

Teh

et al. 2016

Sci Rep

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Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD.

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“…The intake of abundant saturated fatty acids resulted in ERS in the intestines and decreased GLP-1 production [25], suggesting that exogenous GLP-1 may reduce the injury. GLP-1 receptor analog remarkably decreased markers of inflammation, oxidative stress, and fibrosis in the kidneys of maternal obesity mice [26]. GLP-1 decreased BIP and p-eIF2α protection against ER stress-induced cell apoptosis-associated transcription factor CHOP in pancreatic INS-1 cells in Akita mice [23], while Cunha et al [27] reported that GLP-1R treatment increased ATF4-CHOP expression in vitro .…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Glucagon-Like Peptide-1 Analog on Renal Tubular Injury in Mice on High-Fat Diet

Guo

Wang

et al. 2017

Cell Physiol Biochem

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Aims: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). Methods: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured. The expression of endoplasmic reticulum stress (ERS) markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis in the kidney were examined utilizing western blotting, immunohistochemistry and TUNEL, respectively. Angiotensin II and angiotensin II type 1 receptor (AT1R) were examined by ELISA. Human proximal tubule epithelial cells (HK2) were treated with GLP-1(150 nM) followed by treatment with palmitic acid (500 nM [PA]) for 24 h. HK2 cells treated with BSA were used as controls. The protein levels of ERS markers, apoptosis-associated protein, and AT1R were measured by western blotting. Results: Increase of body weight, food intake, and systolic blood pressure was less pronounced in GLP-1 treated HFDG mice compared to HFD mice. The levels of ERS markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis decreased following GLP-1 treatment in vivo and in vitro (p<0.05). Increased AT1R induced by HFD and PA were blocked with GLP-1 treatment. In contrast, the level of angiotensin II after GLP-1 treatment was not significantly different between the HFD and HFDG mice. Conclusion: The study indicated that saturated fatty acids induced ERS and apoptosis in the kidney and increased AT1R expression. GLP-1 treatment exerted renoprotective effects against saturated fatty acid-induced kidney tubular cell ERS and apoptosis together with inhibition of AT1R expression in vivo and in vitro.

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Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity

Cited by 44 publications

References 34 publications

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring

Protective Effects of Glucagon-Like Peptide-1 Analog on Renal Tubular Injury in Mice on High-Fat Diet

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