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Diet-induced obesity and prenatal undernutrition lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei

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Abstract

Previously we reported that prenatal undernutrition (UN) leads to a dysregulation of appetite suppression through alterations in hypothalamic neuropeptide gene expression. In the current study, we expand our observations and investigate neuroendocrine transcriptional responses and central leptin sensitivity within the arcuate nucleus of rats exposed to prenatal UN or a postnatal high-fat diet (HF). Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30 % of AD intake throughout gestation (UN) resulting in either control or intrauterine growth-restricted female offspring. At weaning, AD offspring were fed either a chow (C) or a HF (30 % fat wt/wt) diet ad libitum for the remainder of the study, whereas UN offspring were fed a chow diet only. At ~142 days, AD and UN offspring received either recombinant rat leptin (L) or saline (S) subcutaneously for 14 days. Prenatal UN had a significant effect on hypothalamic NPY (P < 0.0001), AgRP (P < 0.01) and ObRb (P < 0.02) mRNA expression compared to AD chow-fed offspring. A postnatal HF diet had a significant effect on AgRP mRNA expression (P < 0.001), compared to AD chow-fed offspring, but no effect on NPY and ObRb expression. Leptin treatment, in both UN and HF offspring, was ineffective in reducing NPY and AgRP mRNA expression, and had no effect on ObRb expression. These findings suggest that prenatal UN and a postnatal HF diet lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei and reduced sensitivity to leptin’s anorexigenic effects.

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Acknowledgment

This work was supported by grants from the Health Research Council of New Zealand (HRC) and Gravida: National Centre for Growth and Development, a Centre of Research Excellence administered by the New Zealand Tertiary Education Commission.

Author contributions

BHB and MF wrote the grant applications for funding support for the studies. BHB, SK and MV conceptualised and designed all in vivo experimental procedures and research strategies. MF conceptualised the design and implementation of all molecular studies. MF and CKW performed all molecular expression analyses. MF and CKW analysed all molecular data. MF, BHB, SK and MV provided critical interpretation of the results. MF drafted the manuscript. MF, BHB, SF and MV edited and revised the manuscript. All authors have read and approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Physiology, The University of Auckland, Auckland, New Zealand

    Mhoyra Fraser

  2. The Liggins Institute, The University of Auckland, Auckland, New Zealand

    Mhoyra Fraser, Charisma K. Dhaliwal, Mark H. Vickers & Stefan O. Krechowec

  3. Gravida: National Centre for Growth and Development, Auckland, New Zealand

    Mhoyra Fraser, Mark H. Vickers & Bernhard H. Breier

  4. School of Food and Nutrition, College of Health, Massey University, Albany Campus, Auckland, New Zealand

    Bernhard H. Breier

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  1. Mhoyra Fraser
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Correspondence to Mhoyra Fraser.

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The authors have no conflicts of interest to disclose. The study sponsors had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the manuscript for publication. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript.

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Fraser, M., Dhaliwal, C.K., Vickers, M.H. et al. Diet-induced obesity and prenatal undernutrition lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei. Endocrine 53, 839–847 (2016). https://doi.org/10.1007/s12020-016-0918-5

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