Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis

Abstract

Animal models of maternal high fat diet (HFD) demonstrate perturbed offspring metabolism although the effects differ markedly between models. We assessed studies investigating metabolic parameters in the offspring of HFD fed mothers to identify factors explaining these inter-study differences. A total of 171 papers were identified, which provided data from 6047 offspring. Data were extracted regarding body weight, adiposity, glucose homeostasis and lipidaemia. Information regarding the macronutrient content of diet, species, time point of exposure and gestational weight gain were collected and utilized in meta-regression models to explore predictive factors. Publication bias was assessed using Egger's regression test. Maternal HFD exposure did not affect offspring birthweight but increased weaning weight, final bodyweight, adiposity, triglyceridaemia, cholesterolaemia and insulinaemia in both female and male offspring. Hyperglycaemia was found in female offspring only. Meta-regression analysis identified lactational HFD exposure as a key moderator. The fat content of the diet did not correlate with any outcomes. There was evidence of significant publication bias for all outcomes except birthweight. Maternal HFD exposure was associated with perturbed metabolism in offspring but between studies was not accounted for by dietary constituents, species, strain or maternal gestational weight gain. Specific weaknesses in experimental design predispose many of the results to bias.

Keywords: Adiposity; glucose; lipids; maternal; obesity.

Figure 1

Meta‐analysis and meta‐regression of birth weight and wean weight in the male and female offspring of mothers exposed to a high fat diet (HFD) during gestation and lactation. a. Male birth weight, b. male wean weight, c. female birthweight, d. female wean weight. In the TOTAL model, estimated standardized mean differences (SMD) and 95% confidence intervals are presented as a summary of all studies. k refers to the number of studies included. The significance of the effect size was assessed by random‐effects model analysis. Explanation for heterogeneity was explored by meta‐regression by including various moderating factors into the random‐effects model. These included the following: nesting – the use of statistical procedures to account for non‐independence of animals from the same litter; randomization – the random assignment of animals to each intervention group; CD:HFD ratio of macronutrients, fat, carbohydrate (CHO) and protein; cafeteria diet – the use of choice diet or supplementation of standard diets with palatable energy‐rich foods; species; and maternal weight – an approximation for gestation weight gain taken as the ratio change in weight from pre mating to post lactation. Estimates for the SMD and 95% confidence intervals are presented for these models along with the residual heterogeneity unaccounted for in the model (the I^2 beneath each model).

Figure 2

Meta‐analysis and meta‐regression of final body weight and adiposity in the male and female offspring of mothers exposed to a high fat diet (HFD) during gestation and lactation. a. Male body weight, b. male adiposity, c. female body weight d. female adiposity. In the TOTAL model, estimated standardized mean differences (SMD) and 95% confidence intervals are presented as a summary of all studies. k refers to the number of studies included. The significance of the effect size was assessed by random‐effects model analysis. Intra study heterogeneity (as a percentage) is shown as the I^2 value. Explanation for heterogeneity was explored by meta‐regression by including various moderating factors into the random‐effects model. These included the following: nesting – the use of statistical procedures to account for non‐independence of animals from the same litter; randomization – the random assignment of animals to each intervention group; CD:HFD ratio of macronutrients, fat, carbohydrate (CHO) and protein; cafeteria diet – the use of choice diet or supplementation of standard diets with palatable energy‐rich foods; species; the method by which adiposity was assessed, fat pad weights, dual energy X‐ray absorptiometry (DEXA) scan or nuclear magnetic resonance (NMR) scan; and maternal weight – an approximation for gestation weight gain taken as the ratio change in weight from pre mating to post lactation. Estimates for the SMD and 95% confidence intervals are presented for these models along with the residual heterogeneity unaccounted for in the model (the I^2 beneath each model).

Figure 3

Meta‐analysis and meta‐regression of glucose homeostasis in the male and female offspring of mothers exposed to a high fat diet (HFD) during gestation and lactation. a. Male glucose, b. male insulin, c. female glucose, d. female insulin. In the TOTAL model, estimated standardized mean differences (SMD) and 95% confidence intervals are presented as a summary of all studies. k refers to the number of studies included. The significance of the effect size was assessed by random‐effects model analysis. Intra study heterogeneity (as a percentage) is shown as the I^2 value. Explanation for heterogeneity was explored by meta‐regression by including various moderating factors into the random‐effects model. These included the following: nesting – the use of statistical procedures to account for non‐independence of animals from the same litter; randomization – the random assignment of animals to each intervention group; CD:HFD ratio of macronutrients, fat, carbohydrate (CHO) and protein; cafeteria diet – the use of choice diet or supplementation of standard diets with palatable energy‐rich foods; species; the method by which glucose–insulin homeostasis was assessed; and maternal weight – an approximation for gestation weight gain taken as the ratio change in weight from pre mating to post lactation. Estimates for the SMD and 95% confidence intervals are presented for these models along with the residual heterogeneity unaccounted for in the model (the I^2 beneath each model).

Figure 4

Meta‐analysis and meta‐regression of lipidaemia in the male and female offspring of mothers exposed to a high fat diet (HFD) during gestation and lactation. a. Male cholesterol, b. male triglycerides, c. female cholesterol, d. female triglycerides. In the TOTAL model, estimated standardized mean differences (SMD) and 95% confidence intervals are presented as a summary of all studies. k refers to the number of studies included. The significance of the effect size was assessed by random‐effects model analysis. Intra study heterogeneity (as a percentage) is shown as the I^2 value. Explanation for heterogeneity was explored by meta‐regression by including various moderating factors into the random‐effects model. These included the following: nesting – the use of statistical procedures to account for non‐independence of animals from the same litter; randomization – the random assignment of animals to each intervention group; CD:HFD ratio of macronutrients, fat, carbohydrate (CHO) and protein; cafeteria diet – the use of choice diet or supplementation of standard diets with palatable energy‐rich foods; species; and maternal weight – an approximation for gestation weight gain taken as the ratio change in weight from pre mating to post lactation. Estimates for the SMD and 95% confidence intervals are presented for these models along with the residual heterogeneity unaccounted for in the model (the I^2 beneath each model).