Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

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

Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

Nguyen, LT

Saad, S

Tan, Y

Pollock, C Chen, H

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Publication Type:: Journal Article
Citation:: Journal of molecular endocrinology, 2017, 59 (1), pp. 81 - 92
Issue Date:: 2017-07-01

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Field	Value	Language
dc.contributor.author	Nguyen, LT https://orcid.org/0000-0002-0630-4959	en_US
dc.contributor.author	Saad, S https://orcid.org/0000-0001-8067-8046	en_US
dc.contributor.author	Tan, Y https://orcid.org/0000-0001-9221-330X	en_US
dc.contributor.author	Pollock, C	en_US
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.date.available	2020-05-25T19:02:30Z
dc.date.issued	2017-07-01	en_US
dc.identifier.citation	Journal of molecular endocrinology, 2017, 59 (1), pp. 81 - 92	en_US
dc.identifier.uri	http://hdl.handle.net/10453/110105
dc.description.abstract	© 2017 Society for Endocrinology. Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.	en_US
dc.relation.ispartof	Journal of molecular endocrinology	en_US
dc.relation.isbasedon	10.1530/JME-17-0056	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Hypothalamus	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	Obesity	en_US
dc.subject.mesh	Phenylbutyrates	en_US
dc.subject.mesh	Pro-Opiomelanocortin	en_US
dc.subject.mesh	Ubiquitin-Protein Ligases	en_US
dc.subject.mesh	Neuropeptide Y	en_US
dc.subject.mesh	Membrane Glycoproteins	en_US
dc.subject.mesh	Receptor, Melanocortin, Type 4	en_US
dc.subject.mesh	Receptors, Neuropeptide Y	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	HSP40 Heat-Shock Proteins	en_US
dc.subject.mesh	Stress, Physiological	en_US
dc.subject.mesh	Maternal Nutritional Physiological Phenomena	en_US
dc.subject.mesh	Unfolded Protein Response	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.subject.mesh	Autophagy-Related Protein 5	en_US
dc.subject.mesh	Autophagy-Related Protein 7	en_US
dc.title	Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	59	en_US
utslib.for	0707 Veterinary Sciences	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1114 Paediatrics and Reproductive Medicine	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	59	en_US

Abstract:

© 2017 Society for Endocrinology. Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

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http://hdl.handle.net/10453/110105