A systematic review on animal models of maternal high fat feeding and offspring glycaemic control

International Journal of Obesity (2011) 35, 325–335 & 2011 Macmillan Publishers Limited All rights reserved 0307-0565/11 www.nature.com/ijo REVIEW A systematic review on animal models of maternal high fat feeding and offspring glycaemic control H Ainge1, C Thompson2, SE Ozanne3 and KB Rooney1 1 Discipline of Exercise and Sport Science, University of Sydney, Sydney, NSW, Australia; 2Discipline of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia and 3Department of Clinical Biochemistry, Institute of Metabolic Science, Metabolic Research laboratories, University of Cambridge, Cambridge, UK The mechanistic link between obese parents and obese offspring and the relative role of genes, and a shared environment is not completely understood. Animal models help us to differentiate between genetic and environmental factors, and the interaction between the two. However, the willingness of researchers to blend results from multiple models makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we conducted a systematic review of animal models of maternal high fat feeding in an effort to identify the affect on the offspring glycaemic control. Maternal and offspring outcomes are reported in an effort to identify possible relationships to facilitate and focus on future research. We present here data from 11 studies investigating glycaemic control in offspring exposed to a high fat diet (HFD) during maternal gestation only or gestation and lactation. Studies in this review identify a real risk of type 2 diabetes and obesity in male offspring exposed to a maternal HFD. Poor glycaemic control in the offspring appears to be independent of maternal obesity, birth weight or postweaning macronutrient intake. Inconsistencies between studies however, limit our capacity to identify mechanisms for the developmental origin of these diseases in animal models of overnutrition. International Journal of Obesity (2011) 35, 325–335; doi:10.1038/ijo.2010.149; published online 3 August 2010 Keywords: developmental; diabetes; glucose; insulin; origin Introduction Children of obese parents are more than twice as likely to be obese themselves in adulthood.1 Infants of obese mothers show early indicators of obesity predisposition including increased body mass index, elevated body fat content and reduced 24 h energy expenditure.2 Obesity develops from interplay between environment, behavioural choice and genetic predisposition. An energy imbalance between high caloric food intake and low energy expenditure is compounded by altered gene expression of key hormonal signalling pathways and fuel utilization systems. The mechanistic link between obese parents and obese offspring, and the relative role of genes and a shared environment is not yet completely understood. However, recent data suggest that the environment experienced in utero by offspring of obese women may have an important role. Such an environment may include exposure to maternal Correspondence: Dr KB Rooney, Discipline of Exercise and Sport Science, Faculty of Health Sciences, 75 East Street, Lidcombe, NSW, 2141, Australia. E-mail: Received 1 March 2010; revised 10 June 2010; accepted 20 June 2010; published online 3 August 2010 hyperglycaemia and hyperinsulinaemia. For example, it has been shown in humans that maternal hyperglycaemia during pregnancy is associated with a greater risk of obesity in children, independent of birth weight.3,4 There is also evidence to suggest that maternal body composition per se is a driving factor in offspring adiposity5 and hence, obesityassociated plasma markers, such as leptin and plasma lipids may also be relevant. The developmental origins of diseases, such as obesity, cardiovascular disease, type 2 diabetes and increased central adiposity in humans have been known for quite sometime with epidemiological studies, linking early growth to subsequent risk of disease.6 The initial focus was on the increased risk observed in individuals with a lowbirth weight, and thus the role of under nutrition in utero. However, the environmental stimulus surrounding mothers and unborn children today is more likely that of overnutrition before or during gestation, and there is evidence that a very highbirth weight also increases obesity risk.7 Recently, many animal models of maternal overnutrition have been developed for investigations on offspring development, and include among them: intra-fetal infusion of glucose to sheep during late gestation;8 gastric infusions of high fat liquid diet to rats9 and conventional ad libitum feeding of high fat diets (HFD),10–15 HFD supplemented with Glycaemic control in offspring exposed to a maternal high fat diet H Ainge et al 326 sweetened condensed milk16 or a high fat and/or high sugar junk food/cafeteria diet.17–19 In all models of maternal overnutrition, detrimental effects, such as hyperphagia, elevated whole body adiposity, elevated tissue triglyceride content, abnormal glucose homeostasis and reduced insulin sensitivity have been observed in the offspring. In most cases, these phenotypic characteristics of the metabolic syndrome are present regardless of the diet consumed by the offspring during postnatal development.11,17,18 Taken together, these studies identify a real risk of obesity and insulin resistance in offspring of mothers consuming a HFD during pregnancy. Animal models helps us to differentiate between genetic and environmental factors and the interaction between the two factors. However, the willingness of researchers to blend results from multiple models (such as we have in the paragraph above) makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we decided to conduct a systematic review of animal models of maternal high fat feeding to identify the affect of this diet Table 1 Eligibility criteria Inclusion Exclusion Maternal high fat diet (Fat content Diets of unknown dietary composition 430% of total energy content) of protein, fat and carbohydrate. intervention during gestation or gestation and lactation. All obesogenic but non high fat diets (% fat o30% total energy content) All rat studies Diet interventions not lasting the duration of the gestation. Intragastric feeding models. Male offspring fed a standard chow/ Comparison between high fat models control diet post weaning. with no standard control. Low protein diet interventions, maternal under nutrition or intra-uterine growth restriction models. Genetically modified animals (obesity susceptibility/resistance models) All non rodent studies Eligibility criteria used to assess all articles throughout systematic search. Table 2 on offspring glycaemic control. This review reports maternal and offspring outcomes in an effort to identify possible relationships to facilitate and focus on future research. Methods This systematic review was undertaken in accordance w (...truncated)