Animal Foetal Models of Obesity and Diabetes – From Laboratory to Clinical Settings

Abstract

The prenatal period, during which a fully formed newborn capable of surviving outside its mother’s body is built from a single cell, is critical for human development. It is also the time when the foetus is particularly vulnerable to environmental factors, which may modulate the course of its development. Both epidemiological and animal studies have shown that foetal programming of physiological systems may alter the growth and function of organs and lead to pathology in adulthood. Nutrition is a particularly important environmental factor for the pregnant mother as it affects the condition of offspring. Numerous studies have shown that an unbalanced maternal metabolic status (under- or overnutrition) may cause long-lasting physiological and behavioural alterations, resulting in metabolic disorders, such as obesity and type 2 diabetes (T2DM). Various diets are used in laboratory settings in order to induce maternal obesity and metabolic disorders, and to alter the offspring development. The most popular models are: high-fat, high-sugar, high-fat-high-sugar, and cafeteria diets. Maternal undernutrition models are also used, which results in metabolic problems in offspring. Similarly to animal data, human studies have shown the influence of mothers’ diets on the development of children. There is a strong link between the maternal diet and the birth weight, metabolic state, changes in the cardiovascular and central nervous system of the offspring. The mechanisms linking impaired foetal development and adult diseases remain under discussion. Epigenetic mechanisms are believed to play a major role in prenatal programming. Additionally, sexually dimorphic effects on offspring are observed. Therefore, further research on both sexes is necessary.

From lessons on the long‐term effects of the preimplantation environment on later health to a “modified ART‐DOHaD” animal model

“…72 Second, it is important to investigate various "ART-DOHaD" animal models, produced by ART and shown to exhibit longterm effects, 73 integrated into "DOHaD" animal models produced by maternal nutritional imbalance such as under-and overnutrition. 74 Since ART in domestic animals including cattle, sheep, and horses is worldwide used, pre-and peri-natal effects have been studied to resolve ART-associated problems such as low pregnancy rates, prolonged gestation, and fetal overgrowth, also known as the large offspring syndrome (LOS). 73 As a result of studying causative factors, for example, for LOS in cattle, which presents as an aberrant development of the placenta, 75 the inclusion of serum in embryo culture medium and co-culture with oviductal cells were identified mainly to cause abnormal feto-placental development in ruminants.…”

“…First, it is important to study animals presenting mutations involved in the regulation of placental development, in particular those causing intrauterine growth restriction and pre‐eclampsia, 71 as well as mutant animals with type 2 diabetes mellitus and obese phenotypes such as ob / ob mice 72 . Second, it is important to investigate various “ART‐DOHaD” animal models, produced by ART and shown to exhibit long‐term effects, 73 integrated into “DOHaD” animal models produced by maternal nutritional imbalance such as under‐ and overnutrition 74 . Since ART in domestic animals including cattle, sheep, and horses is worldwide used, pre‐ and peri‐natal effects have been studied to resolve ART‐associated problems such as low pregnancy rates, prolonged gestation, and fetal overgrowth, also known as the large offspring syndrome (LOS) 73 .…”

Genetic Obesity in Pregnant Ay Mice Does Not Affect Susceptibility to Obesity and Food Choice in Offspring

“…Taste preferences and the susceptibility to obesity in an obesogenic environment depend on the genotype [ 7 , 8 ] and the conditions of early life of individuals [ 9 ]. It has been shown that in utero environments have a significant effect on the predisposition of offspring to develop obesity later in life [ 10 ], and this effect can significantly differ in offspring of different sexes [ 11 , 12 ]. Maternal obesity and a maternal high-calorie diet during pregnancy and lactation were shown to increase the risk of obesity development in offspring [ 13 , 14 ] and to affect offspring calorie intake and taste preferences [ 15 , 16 , 17 ].…”

Maternal cafeteria diet influences kisspeptin (Kiss1), kisspeptin receptor(Gpr54), and sirtuin (Sirt1) genes, hormonal and metabolic profiles, and reproductive functions in rat offspring in a sex-specific manner

“…Offspring born to CAF mothers have altered body weight and fat content, as well as glucose, insulin, leptin, and triglyceride levels. However, the results of metabolic outcomes vary depending on the used paradigm (e.g., duration of the diet, its contents, time of exposure to the diet), animal species, and sex of offspring (see review [13]).…”