SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet

Nguyen, LT; Chen, H; Pollock, C; Saad, S

SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet

Nguyen, LT

Chen, H

Pollock, C Saad, S

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2017, 7 (1)
Issue Date:: 2017-12-01

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Field	Value	Language
dc.contributor.author	Nguyen, LT https://orcid.org/0000-0002-0630-4959	en_US
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.contributor.author	Pollock, C	en_US
dc.contributor.author	Saad, S https://orcid.org/0000-0001-8067-8046	en_US
dc.date.available	2017-07-12	en_US
dc.date.issued	2017-12-01	en_US
dc.identifier.citation	Scientific Reports, 2017, 7 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115788
dc.description.abstract	© 2017 The Author(s). Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5′-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/s41598-017-08694-4	en_US
dc.subject.mesh	Kidney	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Prenatal Exposure Delayed Effects	en_US
dc.subject.mesh	Obesity	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Sex Factors	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Intra-Abdominal Fat	en_US
dc.subject.mesh	Stress, Physiological	en_US
dc.subject.mesh	AMP-Activated Protein Kinases	en_US
dc.subject.mesh	Sirtuin 1	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.subject.mesh	Forkhead Box Protein O3	en_US
dc.subject.mesh	Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha	en_US
dc.title	SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	7	en_US
utslib.for	0299 Other Physical Sciences	en_US
utslib.for	0301 Analytical Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	7	en_US

Abstract:

© 2017 The Author(s). Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5′-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.

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http://hdl.handle.net/10453/115788