SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption

Nguyen, LT; Chen, H; Mak, C; Zaky, A; Pollock, C; Saad, S

SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption

Nguyen, LT

Chen, H

Mak, C Zaky, A Pollock, C Saad, S

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Publication Type:: Journal Article
Citation:: American Journal of Physiology - Endocrinology and Metabolism, 2018, 315 (2), pp. E196 - E203
Issue Date:: 2018-08-01

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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	Mak, C	en_US
dc.contributor.author	Zaky, A	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	2020-05-25T19:15:27Z
dc.date.issued	2018-08-01	en_US
dc.identifier.citation	American Journal of Physiology - Endocrinology and Metabolism, 2018, 315 (2), pp. E196 - E203	en_US
dc.identifier.issn	0193-1849	en_US
dc.identifier.uri	http://hdl.handle.net/10453/122788
dc.description.abstract	© 2018 the American Physiological Society. Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.	en_US
dc.relation.ispartof	American Journal of Physiology - Endocrinology and Metabolism	en_US
dc.relation.isbasedon	10.1152/ajpendo.00472.2017	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Hepatocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Animals, Newborn	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Prenatal Exposure Delayed Effects	en_US
dc.subject.mesh	Insulin Resistance	en_US
dc.subject.mesh	Obesity	en_US
dc.subject.mesh	Body Weight	en_US
dc.subject.mesh	Leptin	en_US
dc.subject.mesh	Alanine Transaminase	en_US
dc.subject.mesh	Anti-Obesity Agents	en_US
dc.subject.mesh	Diet	en_US
dc.subject.mesh	Cell Size	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Lipid Metabolism	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.subject.mesh	Chemical and Drug Induced Liver Injury	en_US
dc.subject.mesh	Heterocyclic Compounds, 4 or More Rings	en_US
dc.title	SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	315	en_US
utslib.for	0606 Physiology	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	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	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	315	en_US

Abstract:

© 2018 the American Physiological Society. Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.

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http://hdl.handle.net/10453/122788