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Cited by 16Regulation of Appetite and ObesityBirth, Development, and HealthHypothalamic control of reproductive hormones

Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat

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Vargas, Vladimir E., Gurung, Sunam, Grant, Benjamin, Hyatt, Kimberly, Singleton, Krista, Myers, Sarah M., Saunders, Debra, Njoku, Charity +2 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0185272PMC PMC5619766
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Abstract

The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

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  • The increased offspring adiposity following gestational hypoxia is related to elevated expression of pro-inflammatory markers in the adipose tissue of hypoxia-exposed rodent offspring compared to normoxic counterparts.

    “This was related to an elevated expression of pro-inflammatory markers in the adipose tissue of hypoxia exposed rodent offspring compared to their normoxic counterparts [100].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [100]

    The Discussion links greater abdominal adiposity in male offspring exposed to gestational hypoxia with greater adipose inflammation. The Results qualify the comparison: elevated cytokine expression was found in peritoneal fat, not subcutaneous fat, and the significant increases in IL-1β and TNFα occurred in hypoxia-exposed offspring fed a high-fat diet compared with normoxic offspring fed a control diet. The claim omits those tissue and diet qualifications. (LLM, conf=0.86)

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  • Exposure to hypoxia during gestation is linked to increased offspring adiposity in adulthood.

    “In the studies available (Table 4), exposure to hypoxia during gestation was linked to increased offspring adiposity in adulthood [100, 101].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [100]

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Cited by

Sorted by citations

Authors
Vargas, V. E., Gurung, S., Grant, B., Hyatt, K., Singleton, K., Myers, S. M., Saunders, D., Njoku, C., Towner, R., & Myers, D. A.
Affiliations
  • University of Oklahoma Health Sciences Center (US)
  • Oklahoma Medical Research Foundation (US)
Corresponding author
Myers, Dean A.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-09-28
Volume
12
Issue
9
Pages
e0185272
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0185272
PMC
PMC5619766
OpenAlex
W2759276418
Cited by
16
References
0
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (NIH R01-HD050620)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
gestational hypoxia, hyperphagia, offspring obesity, hypothalamic arcuate nucleus, paraventricular nucleus, appetite regulation, abdominal fat, adipose tissue cytokines, high-fat diet, developmental programming, c-fos, leptin
MeSH terms
Adipose Tissue, alpha-MSH, Animals, Animals, Newborn, Hypoxia, Anxiety, Arcuate Nucleus of Hypothalamus, Behavior, Animal, Diet, Fear, Feeding Behavior, Female, Hyperphagia, Magnetic Resonance Imaging, Male, Motor Activity, Obesity, Pregnancy, Tumor Necrosis Factor-alpha, Water, Weaning, Interleukin-6, Rats, Sprague-Dawley, Maze Learning, Fetal Weight, Leptin, Maternal Nutritional Physiological Phenomena, Interleukin-1beta

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