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Maternal nutrition can rapidly rescue a nephron deficit in low birthweight offspring
Luise A Cullen-McEwen1, Sarah E Gazzard2, Gessica Gonçalves2
1Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia. luise.cullen-mcewen@monash.edu.
Insights
Maternal high-fat diet post-birth boosts offspring kidney nephron endowment. This dietary strategy can also rescue nephron deficits, potentially reducing chronic kidney disease risk.
Area of Science:
- Nephrology
- Developmental Biology
- Nutritional Science
Background:
- Low birthweight is linked to hypertension and chronic kidney disease.
- Kidney nephron endowment is established early and permanent.
- Strategies to enhance nephron endowment may prevent chronic diseases.
Purpose of the Study:
- To investigate if maternal diet modification post-birth can influence offspring nephron endowment.
- To determine if postnatal dietary changes can rescue nephron deficits.
- To explore the impact of maternal macronutrient balance on nephrogenesis.
Main Methods:
- Mice dams were fed specific diets (high-fat, low-protein) during gestation and/or lactation.
- Offspring nephron endowment was quantified.
- Maternal caloric and macronutrient intake was monitored.
Main Results:
- Switching dams to a high-fat diet at birth augmented offspring nephron endowment by 14%.
- A high-fat diet initiated at birth rescued a 20% nephron deficit caused by maternal low-protein diet during gestation.
- Dietary changes correlated with increased maternal caloric and fat intake and decreased carbohydrate intake postnatally.
Conclusions:
- Maternal diet composition, particularly macronutrient balance, is critical for establishing adequate nephron endowment.
- Postnatal dietary interventions can augment or rescue nephron endowment.
- These findings suggest potential strategies to mitigate kidney disease risk associated with low birthweight.
Abstract:
Low birthweight is a risk factor for hypertension and chronic kidney disease. Kidneys of low birthweight babies typically have a low nephron endowment, which is permanent. Therefore, strategies to boost or rescue nephron endowment in low birthweight offspring might be expected to decrease the prevalence of these chronic conditions. We previously reported that a high-fat diet (17% protein, 43% carbohydrate, 40% fat) fed to mice before mating and until weaning boosted nephron endowment in mice by 20%. Here, we show that offspring from dams fed a normal diet during pregnancy and switched to a high-fat diet at birth had a 14% augmented nephron endowment. Additionally, transition to a high-fat diet at birth completely rescued a 20% nephron deficit induced by feeding dams a low-protein diet (8% protein, 76% carbohydrate, 16% fat) during gestation. The augmentation and rescue of nephron endowment were associated with increased maternal caloric intake on day 1, as well as increased maternal fat and reduced carbohydrate intake during the postnatal period of rapid nephrogenesis. These findings indicate that the balance between the three macronutrients in the maternal diet, both pre- and postnatally, is crucial for nephron endowment.
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