Effects of high fat diet exposure during fetal life on type 2 diabetes development in the progeny

Donatella Gniuli, Alessandra Calcagno, Maria Emiliana Caristo, Alessandra Mancuso, Veronica Macchi, Geltrude Mingrone, and Roberto Vettor

Istituto di Medicina Interna, Universita' Cattolica del Sacro Cuore, Rome, Italy 00168

Corresponding Author: dgniuli{at}gmail.com

Nutrition during fetal life is a critical factor contributing to diabetes development in the adulthood. Aim of our study was to verify: 1) whether a high fat diet (HFD) in young adult mice induces alterations of ß-cell mass, proliferation, neogenesis and apoptosis; as well as of insulin sensitivity and secretion; 2) whether these alterations may be reversible after HFD suspension; 3) the effects in a first (F1) and second generation (F2) of mice without direct exposure to HFD after the birth. Type 2 diabetes developed in adult mice on HFD, in F1 mice, HFD-exposed during the fetal or neonatal life, and in F2 mice, whose mothers were HFD-exposed during their fetal life. -cell mass, replication and neogenesis were high in HFD-exposed mice and decreased after diet suspension. -cell mass and replication remained high in F1 mice and decreased in F2 mice whose mothers were exposed to HFD. -cell neogenesis was present in adult mice on HFD and in F1 mice HFD-exposed during fetal and/or neonatal life. We conclude that HFD during fetal life, particularly if combined with the same insult during the suckling period, can induce the type 2 diabetes phenotype, that can be directly transmitted to the progeny even in absence of additional dietary insults.

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