Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents

Chen, H; Simar, D; Pegg, K; Saad, S; Palmer, C; Morris, MJ

Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents

Chen, H

Simar, D Pegg, K Saad, S

Palmer, C Morris, MJ

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Publication Type:: Journal Article
Citation:: Diabetologia, 2014, 57 (3), pp. 614 - 622
Issue Date:: 2014-03-01

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Field	Value	Language
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.contributor.author	Simar, D	en_US
dc.contributor.author	Pegg, K	en_US
dc.contributor.author	Saad, S https://orcid.org/0000-0001-8067-8046	en_US
dc.contributor.author	Palmer, C	en_US
dc.contributor.author	Morris, MJ	en_US
dc.date.available	2013-11-14	en_US
dc.date.issued	2014-03-01	en_US
dc.identifier.citation	Diabetologia, 2014, 57 (3), pp. 614 - 622	en_US
dc.identifier.issn	0012-186X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/30354
dc.description.abstract	Aims/hypothesis: Maternal obesity leads to increased adiposity, hyperlipidaemia and glucose intolerance in offspring. The analogue of glucagon-like peptide-1, exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce body fat and improve metabolic disorders in offspring from obese dams, especially those consuming a high-fat diet (HFD). Methods: Female Sprague Dawley rats were fed chow or an HFD for 5 weeks before mating, and throughout gestation and lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto chow or HFD and those from chow-fed mothers were fed chow. Within each dietary group, half of the pups were injected with Ex-4 (15 μg/kg/day i.p.) for 6 weeks, while the other half received saline. Results: Maternal obesity alone or combined with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia, hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite regulators by glucose in offspring, while glucose intolerance was only observed in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity, hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also restored glucose tolerance and the lipid-lowering effect of blood glucose. However, Ex-4 did not change hypothalamic appetite regulation or the response of appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine expression was significantly reduced by Ex-4. Conclusions/interpretation: Ex-4 reversed the detrimental impact of maternal obesity on lipid and glucose metabolism in offspring regardless of diet, supporting its potential application in reducing metabolic disorders in high-risk populations. © 2013 Springer-Verlag Berlin Heidelberg.	en_US
dc.relation.ispartof	Diabetologia	en_US
dc.relation.isbasedon	10.1007/s00125-013-3132-5	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Hypothalamus	en_US
dc.subject.mesh	Venoms	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Animals, Newborn	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Rats, Sprague-Dawley	en_US
dc.subject.mesh	Hyperglycemia	en_US
dc.subject.mesh	Insulin Resistance	en_US
dc.subject.mesh	Overnutrition	en_US
dc.subject.mesh	Body Weight	en_US
dc.subject.mesh	Blood Glucose	en_US
dc.subject.mesh	Peptides	en_US
dc.subject.mesh	Hypoglycemic Agents	en_US
dc.subject.mesh	Glucose Tolerance Test	en_US
dc.subject.mesh	Weaning	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Maternal Nutritional Physiological Phenomena	en_US
dc.subject.mesh	Adiposity	en_US
dc.subject.mesh	Appetite Regulation	en_US
dc.subject.mesh	Biomarkers	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.subject.mesh	Exenatide	en_US
dc.title	Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	57	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1114 Paediatrics and Reproductive Medicine	en_US
utslib.for	1117 Public Health and Health Services	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	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	57	en_US

Abstract:

Aims/hypothesis: Maternal obesity leads to increased adiposity, hyperlipidaemia and glucose intolerance in offspring. The analogue of glucagon-like peptide-1, exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce body fat and improve metabolic disorders in offspring from obese dams, especially those consuming a high-fat diet (HFD). Methods: Female Sprague Dawley rats were fed chow or an HFD for 5 weeks before mating, and throughout gestation and lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto chow or HFD and those from chow-fed mothers were fed chow. Within each dietary group, half of the pups were injected with Ex-4 (15 μg/kg/day i.p.) for 6 weeks, while the other half received saline. Results: Maternal obesity alone or combined with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia, hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite regulators by glucose in offspring, while glucose intolerance was only observed in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity, hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also restored glucose tolerance and the lipid-lowering effect of blood glucose. However, Ex-4 did not change hypothalamic appetite regulation or the response of appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine expression was significantly reduced by Ex-4. Conclusions/interpretation: Ex-4 reversed the detrimental impact of maternal obesity on lipid and glucose metabolism in offspring regardless of diet, supporting its potential application in reducing metabolic disorders in high-risk populations. © 2013 Springer-Verlag Berlin Heidelberg.

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http://hdl.handle.net/10453/30354