Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys

Author:

McClelland Connie1,Holland Olivia J.12ORCID,Shrestha Nirajan1ORCID,Jukes Claire L.3,Brandon Anna E.3,Cuffe James S. M.4ORCID,Perkins Anthony V.15ORCID,McAinch Andrew J.67ORCID,Hryciw Deanne H.28ORCID

Affiliation:

1. School of Pharmacy and Medical Science, Griffith University, Southport, QLD 4222, Australia

2. Women’s Newborn and Childrens Services, Gold Coast Hospital and Health Service, Southport, QLD 4215, Australia

3. School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia

4. School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia

5. School of Health, University of Sunshine Coast, Sippy Downs, QLD 4556, Australia

6. Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia

7. Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, St. Albans, VIC 3021, Australia

8. Griffith Institute of Drug Discovery, Griffith University, Nathan, QLD 4111, Australia

Abstract

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.

Funder

Griffith University International Postgraduate Research Scholarship

Griffith University Postgraduate Research Scholarship

Griffith Health Top Up Scholarship

Allen Foundation

Publisher

MDPI AG

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