Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring.
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.
Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.|Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, Australia.
Sarah J
SJ
Glastras
School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia.
Michael
M
Tsang
Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
Rachel
R
Teh
School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia.
Hui
H
Chen
Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, Australia.
Rachel T
RT
McGrath
Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
Amgad A
AA
Zaky
Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
Carol A
CA
Pollock
Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
Sonia
S
Saad
D000818:Animals; D015415:Biomarkers / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced* / Q000503:physiopathology; D018384:Oxidative Stress; D011247:Pregnancy; D011897:Random Allocation; D013311:Streptozocin
D015415:Biomarkers; D013311:Streptozocin