Maternal Immunization Affects In Utero Programming of Insulin Resistance and Type 2 Diabetes

Claudia Eberle, Esther Merki, Tomoya Yamashita, Susie Johnson, Aaron M. Armando, Oswald Quehenberger, Claudio Napoli, Wulf Palinski

Research output: Contribution to journalArticle

Abstract

Maternal immunization with oxidized lipoproteins prior to pregnancy protects against atherogenic in utero programming by gestational hypercholesterolemia and enhances beneficial lymphocyte-dependent immune responses in offspring. To determine whether in utero programming and immunomodulation also affect insulin resistance (IR) and type 2 diabetes, we investigated the effects of immunization on glucose and insulin responses in LDL receptor-deficient mice fed regular or 60% sucrose diets, as well as in offspring fed 0.5% cholesterol or 60% sucrose diets. IR was assessed by fasting glucose and insulin levels, oral glucose tolerance tests, glucose clamps, pancreatic immunohistochemistry and plasma free fatty acid concentrations. Immunizations improved glucose responses in both genders and protected both immunized mice and their offspring against IR and type 2 diabetes. Protection occurred even under euglycemic conditions, but was greatest in obese males exposed to very obesogenic/diabetogenic conditions. Hyperinsulinemic euglycemic clamps confirmed that maternal immunization protected mainly by reducing IR, but pancreatic immunocytochemistry also indicated some protection against beta cell damage. Maternal immunization was associated with marked regulation in offspring of 4 genes relevant to diabetes and 19 genes of importance for oxidative stress, as well as increased hepatic activities of key antioxidant enzymes. These findings establish that targeted immunomodulation may be used to protect immunized subjects and their offspring against IR and type 2 diabetes, and thus to reduce cardiovascular risk. They also support the notion that in utero programming influences offspring disease not by a single mechanism, but by multiple systemic effects.

Original languageEnglish
Article numbere45361
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 18 2012

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Eberle, C., Merki, E., Yamashita, T., Johnson, S., Armando, A. M., Quehenberger, O., Napoli, C., & Palinski, W. (2012). Maternal Immunization Affects In Utero Programming of Insulin Resistance and Type 2 Diabetes. PLoS One, 7(9), [e45361]. https://doi.org/10.1371/journal.pone.0045361