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Cited by 13Birth, Development, and HealthAdipokines, Inflammation, and Metabolic DiseasesGestational Diabetes Research and Management

Insulin-signalling dysregulation and inflammation is programmed trans-generationally in a female rat model of poor maternal nutrition

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Tarry-Adkins, Jane L., Aiken, Catherine E., Ashmore, Thomas J., Ozanne, Susan E.·2018·Scientific Reports
DOI 10.1038/s41598-018-22383-wPMC PMC5838091
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Abstract

Developmental programming phenotypes can be recapitulated in subsequent generations not directly exposed to the initial suboptimal intrauterine environment. A maternal low-protein diet during pregnancy and postnatal catch-up growth (‘recuperated’) alters insulin signaling and inflammation in rat offspring (F1-generation). We aimed to establish if this phenotype is also present in F2-generation females. Insulin-receptor-substrate-1 protein expression was decreased in para-ovarian adipose tissue at 3 months in offspring exposed to a grand-maternal low-protein diet (F2-recuperated), vs. F2-control animals (p < 0.05). There was no effect of grand-maternal diet upon Insulin-receptor-substrate-1 mRNA. Protein-kinase C-zeta protein levels were increased at 3 and 6 months in F2-recuperated animals (p < 0.01 at both ages). Phosphorylated-Akt ser473 levels were decreased in F2-recuperated animals (p < 0.001). Interleukin-1β protein levels were increased at 3 (p < 0.01) and (p < 0.001) 6 months in F2-recuperated animals. Vastus-lateralis insulin-receptor-β protein expression (p < 0.001) and pAkt ser473 (p < 0.01) were increased at 3 months in F2-recuperated animals compared to controls. At 6 months, PAkt ser473 was lower in F2-recuperated animals (p < 0.001). Aspects of insulin signalling dysregulation and inflammation present in offspring of low-protein fed dams can be transmitted to subsequent generations without further exposure to a suboptimal maternal diet. These findings contribute to our understanding of insulin-resistance in grandchildren of sub-optimally nourished individuals during pregnancy.

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  • Across the species surveyed, changes in offspring adiposity are accompanied by alterations in adipocyte size or number, insulin signaling and metabolic protein levels, including PPARγ, as well as inflammatory markers and leukocytes in the adipose tissue of the offspring born from low protein diet-fed mothers.

    “Across the species surveyed, changes in offspring adiposity are accompanied by alterations in adipocyte size or number, insulin signaling and metabolic protein levels, including PPARγ, as well as inflammatory markers and leukocytes in the adipose tissue of the offspring born from low protein diet-fed mothers [71, 72, 78, 82].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [72]

    The Results (Anthropomorphic measurements; insulin-signalling and pro-inflammatory marker sections) report increased para-ovarian fat-pad weight, a shift in the proportion of small adipocytes, altered insulin-signalling proteins, and increased IL-1β in female F2 rats exposed to grand-maternal protein restriction. Mean adipocyte size did not change, and the paper does not establish the sentence’s claims about PPARγ, adipose-tissue leukocytes, or effects across species. (LLM, conf=0.88)

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  • Overall, the available data suggest that maternal low protein diets have a complex effect on adipose tissue biology, with studies finding divergent molecular changes.

    “Overall, the available data suggest that maternal low protein diets have a complex effect on adipose tissue biology, with studies finding divergent molecular changes [71, 72].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [72]

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Cited by

Sorted by citations

Authors
Tarry-Adkins, J. L., Aiken, C. E., Ashmore, T. J., & Ozanne, S. E.
Affiliations
University of Cambridge (GB)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-03-05
Volume
8
Issue
1
Pages
4014-4014
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-22383-w
PMC
PMC5838091
OpenAlex
W2806618813
Cited by
13
References
2
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 1
FWCI
2.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (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)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • International Seafood Sustainability Foundation
  • British Heart Foundation (PG/09/037/27387, FS/09/029/27902)
  • Academy of Medical Sciences (AMS-SGCL11-AikenC)
  • Isaac Newton Trust
  • Medical Research Council (MC_ UU_12012/4, MC_UU_00014/4)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
developmental programming, maternal low-protein diet, catch-up growth, insulin signaling, insulin resistance, inflammation, IRS-1, protein kinase C zeta, Akt phosphorylation, IL-1β, insulin receptor beta, female offspring, rat model
MeSH terms
Animals, Blood Glucose, Female, Inflammation, Insulin, Insulin Resistance, Pregnancy, Signal Transduction, Rats, Wistar, Muscle, Skeletal, Inflammation Mediators, Models, Animal, Maternal Nutritional Physiological Phenomena, Rats

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