Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

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  • Author(s): Desai M;Desai M; Han G; Han G; Ross MG; Ross MG
  • Source:
    Appetite [Appetite] 2016 Apr 01; Vol. 99, pp. 193-199. Date of Electronic Publication: 2016 Jan 16.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: England NLM ID: 8006808 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8304 (Electronic) Linking ISSN: 01956663 NLM ISO Abbreviation: Appetite Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, New York, Academic Press.
    • Subject Terms:
      Maternal Nutritional Physiological Phenomena*; Hyperphagia/*physiopathology ; Hypothalamus/*metabolism ; Malnutrition/*physiopathology; Adiposity ; Agouti-Related Protein/genetics ; Agouti-Related Protein/metabolism ; Animals ; Animals, Newborn ; Appetite/physiology ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Body Weight ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; Diet, High-Fat ; Energy Intake ; Epigenesis, Genetic ; Female ; Hyperphagia/etiology ; Hyperphagia/genetics ; Male ; Malnutrition/complications ; Malnutrition/genetics ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Obesity/etiology ; Obesity/genetics ; Obesity/physiopathology ; Pregnancy ; Rats ; Satiation/physiology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Transcription Factor HES-1/genetics ; Transcription Factor HES-1/metabolism
    • Abstract:
      Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring.
      (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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    • Grant Information:
      R01 DK081756 United States DK NIDDK NIH HHS; R21 ES023112 United States ES NIEHS NIH HHS; R01DK081756 United States DK NIDDK NIH HHS; R21ES023112-01 United States ES NIEHS NIH HHS
    • Contributed Indexing:
      Keywords: Energy sensors; Epigenetic factors; bHLH genes
    • Accession Number:
      0 (AGRP protein, rat)
      0 (Agouti-Related Protein)
      0 (Ascl1 protein, rat)
      0 (Basic Helix-Loop-Helix Transcription Factors)
      0 (Hes1 protein, rat)
      0 (Nerve Tissue Proteins)
      0 (Neurog3 protein, rat)
      0 (Transcription Factor HES-1)
      EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
      EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
      EC 2.1.1.37 (Dnmt1 protein, rat)
      EC 2.7.1.1 (mTOR protein, rat)
      EC 2.7.11.1 (TOR Serine-Threonine Kinases)
    • Publication Date:
      Date Created: 20160120 Date Completed: 20161213 Latest Revision: 20211203
    • Publication Date:
      20231215
    • Accession Number:
      PMC4813304
    • Accession Number:
      10.1016/j.appet.2016.01.023
    • Accession Number:
      26785315