A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue

Faria, Juliana de Almeida; Duque-Guimarães, Daniella E.; Carpenter, Asha A. M.; Loche, Elena; Ozanne, Susan E.

doi:10.1038/srep44949

Cited by 27 publications

(21 citation statements)

References 29 publications

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“…Male offspring exposed to maternal obesity during suckling also displayed a minor effect of lower gonadal mRNA expression of AKT2 at 4 weeks, and IRS2 at 12 weeks, an upstream activator of PI3K. Whilst white adipose tissue only accounts for a small amount of glucose uptake, it is susceptible to insulin resistance due to adverse maternal nutrition in offspring 16,49 . One limitation of the current study was that we only considered mRNA and not protein expression.…”

Section: Discussionmentioning

confidence: 99%

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats

George

Draycott

Muir

et al. 2019

Sci Rep

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Exposure to maternal obesity during early development programmes adverse metabolic health in rodent offspring. We assessed the relative contributions of obesity during pregnancy and suckling on metabolic health post-weaning. Wistar rat offspring exposed to control (C) or cafeteria diet (O) during pregnancy were cross-fostered to dams on the same (CC, OO) or alternate diet during suckling (CO, OC) and weaned onto standard chow. Measures of offspring metabolic health included growth, adipose tissue mass, and 12-week glucose and insulin concentrations during an intraperitoneal glucose tolerance test (ipGTT). Exposure to maternal obesity during lactation was a driver for reduced offspring weight post-weaning, higher fasting blood glucose concentrations and greater gonadal adiposity (in females). Males displayed insulin resistance, through slower glucose clearance despite normal circulating insulin and lower mRNA expression of PIK3R1 and PIK3CB in gonadal fat and liver respectively. In contrast, maternal obesity during pregnancy up-regulated the insulin signalling genes IRS2 , PIK3CB and SREBP1-c in skeletal muscle and perirenal fat, favouring insulin sensitivity. In conclusion exposure to maternal obesity during lactation programmes offspring adiposity and insulin resistance, overriding exposure to an optimal nutritional environment in utero , which cannot be alleviated by a nutritionally balanced post-weaning diet.

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Section: Discussionmentioning

confidence: 99%

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats

George

Draycott

Muir

et al. 2019

Sci Rep

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“…Adipose tissue has been shown to be an important target of developmental programming in animal models of both maternal undernutrition and overnutrition. In studies carried out only in male offspring and, specifically, in the epididymal white adipose tissue (eWAT), both maternal undernutrition [102] and maternal obesity [103] program an adipose tissue-insulin resistant phenotype accompanied by increased adiposity [102, 104, 105]. These programmed changes have both been attributed to epigenetic changes in adipose tissue.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Importantly, an increase in adipose tissue miR-483 and parallel reduction in growth differentiation factor 3 (GDF-3) was also observed in adipose tissue from humans with low birthweight, showing conservation of this programmed mechanism. Programmed changes in miRNAs were also observed in a mouse model of maternal diet-induced obesity [103, 105]. Maternal feeding of a high-fat and high-simple-carbohydrate diet led to a programmed increase in miR-126, which led to a reduction in its direct target, insulin receptor substrate-1 (IRS-1), in eWAT of male offspring [103].…”

Section: Animal Studiesmentioning

confidence: 99%

Intrauterine programming of obesity and type 2 diabetes

et al. 2019

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The type 2 diabetes epidemic and one of its predisposing factors, obesity, are major influences on global health and economic burden. It is accepted that genetics and the current environment contribute to this epidemic; however, in the last two decades, both human and animal studies have consolidated considerable evidence supporting the 'developmental programming' of these conditions, specifically by the intrauterine environment. Here, we review the various in utero exposures that are linked to offspring obesity and diabetes in later life, including epidemiological insights gained from natural historical events, such as the Dutch Hunger Winter, the Chinese famine and the more recent Quebec Ice Storm. We also describe the effects of gestational exposure to endocrine disruptors, maternal infection and smoking to the fetus in relation to metabolic programming. Causal evidence from animal studies, motivated by human observations, is also discussed, as well as some of the proposed underlying molecular mechanisms for developmental programming of obesity and type 2 diabetes, including epigenetics (e.g. DNA methylation and histone modifications) and microRNA interactions. Finally, we examine the effects of non-pharmacological interventions, such as improving maternal dietary habits and/or increasing physical activity, on the offspring epigenome and metabolic outcomes.

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“…Children born to obese women are more likely to be exposed to the same obesogenic environment growing up, 23 which implies that CVD risk may be further modified by the quality of postnatal life. In rodents, a post-weaning obesogenic diet has been reported to exacerbate the detrimental effects of maternal diet-induced obesity on offspring body weight gain, 24 , 25 lipid metabolism, 26 insulin sensitivity, 16 , 27 and endothelial dysfunction. 28 However, whether an additional exposure to a calorie-rich postnatal environment worsens the programmed cardiac effects on the adult offspring of a maternal obesogenic diet is relatively unexplored in any species.…”

Section: Introductionmentioning

confidence: 99%

Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet

Loche

Blackmore

Carpenter

et al. 2018

Cardiovascular Research

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AimsObesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity.Methods and resultsThe impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure, and function was assessed in 8-week-old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001); maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002) increased absolute heart weight; maternal obesity (P = 0.01) and offspring obesity (P = 0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these genes were not affected by offspring diet; maternal obesity (P = 0.02); and offspring obesity (P = 0.05) caused hypertension and effects were additive.ConclusionsMaternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes, and remodelling of cardiac structure. These data highlight that the perinatal period is just as important as adult-onset obesity in predicting CVD risk. Therefore, early developmental periods are key intervention windows to reduce the prevalence of CVD.

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A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue

Cited by 27 publications

References 29 publications

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats

Intrauterine programming of obesity and type 2 diabetes

Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet

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