SIRT1 ATTENUATES KIDNEY DISORDERS IN OFFSPRING DUE TO MATERNAL HIGH-FAT FEEDING

L NGUYEN1, C MAK2,  H CHEN2, A ZAKY1, C POLLOCK1, S SAAD1
1KOLLING INSTITUTE, ST. LEONARDS, AUSTRALIA, 2UNIVERSITY OF TECHNOLOGY, SYDNEY, ULTIMO, AUSTRALIA

Background: Maternal high-fat feeding (MHF) has been associated with kidney damage and dysfunction in male offspring. Our previous study suggested that the downregulation of Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, might underline the effect.
Aim: We aimed to test the hypothesis that SIRT1 overexpression or activation in the offspring early in life can attenuate kidney disorders due to MHF.
Methods: Diet-induced obese female C57BL/6 mice were crossed with heterozygous SIRT1-transgenic (Tg) male mice to produce both Wild-type (WT) and Tg offspring. Alternatively, SIRT1 activator SRT1720 (25mg/kg/2days i.p) was administrated in WT offspring from week 3 to week 9 of age. Offspring mice were studied at weaning or postnatal week 9 and examined for metabolic and kidney disorders.
Results: Perinatal SIRT1 overexpression improved MHF offspring’s metabolic profiles and kidney antioxidant capacity, while suppressing inflammation and fibrotic markers. SRT1720 administration in MHF offspring weaned on the high-fat diet also improved glucose homeostasis and attenuated renal lipotoxicity, oxidative stress, and fibrogenesis markers, suggesting attenuated kidney disorders in the animals. Urinary albumin creatinine ratio, however, was not improved.
Conclusion: The findings support the important roles of SIRT1 in fetal programming and suggest that SIRT1 therapy can mitigate the development of chronic kidney diseases early in life due to maternal obesity.


Biography:
Long Nguyen recently completed his PhD in Prof. Carol Pollock’s lab at the Kolling Institute. He is interested in studying the etiology of metabolic disorders, especially in regard to fetal programming. His current research focuses on Sirt1, a metabolic sensor involved in caloric restriction and senescence.

About ANZSN

The ASM is hosted by Australian and New Zealand Society of Nephrology.

The aims of the Society are to promote and support the study of the kidney and urinary tract in health and disease, and to ensure the highest professional standards for the practice of nephrology in Australia and New Zealand.

Conference Managers

Please contact the team at Conference Design with any questions regarding the Annual Scientific Meeting

© 2015 - 2016 Conference Design Pty Ltd