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

Abstract

SummaryAnimal 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.

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

“…Our findings are in line with a systematic review of animal experiments showing that a maternal obesogenic diet during pregnancy negatively affects offspring's body weight, body composition, and glucose homeostasis . Effect sizes from a meta‐regression of maternal high‐fat diet during pregnancy on offspring adult body weight, adiposity, total cholesterol, triglycerides, and insulin were in the same direction and magnitude as our findings; however, in contrast to our findings, there was no statistically significant difference for glucose in males . Similar to these animal systematic reviews, but in contrast to human studies, no effect of maternal obesity on birth weight was found.…”

“…Further, we performed pre‐specified subgroup analyses for age and species of the offspring, but these factors also did not explain the heterogeneity. Other factors, such as the maternal diet during lactation and timing of exposure, may explain the variation observed . Standardizing dietary composition and duration and intensity of maternal obesity induction might reduce this form of heterogeneity and may help unravel modifying factors of the effect of maternal obesity on the offspring …”

“…While valuable, they can be hindered by subjective selection and lack of appropriate publication bias assessment . Existing systematic reviews of animal experiments focused on the effect of an obesogenic diet at any time during gestation instead of focusing on the effects of maternal obesity already present prior to conception . Animals models where obesity is present before and during pregnancy are more reflective of the offspring effects in conceiving women with obesity.…”

“…13 Existing systematic reviews of animal experiments focused on the effect of an obesogenic diet at any time during gestation instead of focusing on the effects of maternal obesity already present prior to conception. 14,15 Animals models where obesity is present before and during pregnancy are more reflective of the offspring effects in conceiving women with obesity. Our objective was to systematically review the available evidence provided by animal experiments on the effect of maternal obesity before and during pregnancy on offspring's anthropometry, cardiovascular, and metabolic outcomes.…”

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

“…Surprisingly, however, very little is known about the consequences of maternal and early‐life exposure to a diet highly rich in fat and sugar on the developing offspring. While several studies have described the metabolic effects of maternal obesity on offspring, the effects of overnutrition without the confounding factor of maternal obesity are still missing. To investigate the effect of maternal overnutrition rather than obesity, therefore, we maintained our dams on an HFSD starting on gestational day 2 and then throughout pregnancy.…”