Diet-induced obesity in gravid rats engenders early hyperadiposity in the offspring

Caluwaerts, Silvia; Lambin, Suzan; Bree, Rieta Van; Peeters, H; Vergote, Ignace; Verhaeghe, Johan

doi:10.1016/j.metabol.2007.06.007

Cited by 48 publications

(35 citation statements)

References 36 publications

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“…In the current studies, the animals were fed a diet that derived 35% of its calories from fat and was also high in total calories; this diet is similar to the typical American diet (71). Several studies in rodents have also investigated the effects of a maternal HFD on the development of metabolic abnormalities in the offspring (21,24,(72)(73)(74)(75)(76)(77)(78)(79). While these studies describe a broad range of metabolic abnormalities, only a few describe increased TGs in the liver of adult offspring of pregnant rats fed a HFD; however, none of them determined whether the fatty liver develops prior to or after the development of obesity.…”

Section: Discussionmentioning

confidence: 99%

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

McCurdy¹,

Bishop²,

Williams³

et al. 2009

J. Clin. Invest.

420

562

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Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.

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Section: Discussionmentioning

confidence: 99%

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

McCurdy¹,

Bishop²,

Williams³

et al. 2009

J. Clin. Invest.

420

562

View full text Add to dashboard Cite

show abstract

“…Previous studies in rats have demonstrated that the majority of body fat is located in subcutaneous deposits at the time of weaning (subcutaneous fat weight increases 6-fold). Two months later, the majority of body fat is located in the abdominal cavity (intra-abdominal fat increases 116-fold) [32] . Therefore, it can be assumed that the "catch-up" growth of IUGR pups after weaning may contribute to the greater accumulation of abdominal fat and favor a later-stage metabolic dysfunction in IUGR rats.…”

Section: Discussionmentioning

confidence: 99%

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Xia

Shen

et al. 2013

Acta Pharmacol Sin

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Aim: Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods: Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results: UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion: PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.

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“…23 Pups from obese dams would receive higher levels of nutrients, such as triglycerides, from the maternal circulation to support their growth. Interestingly, unchanged or lower birth weight has been observed in offspring from obese mothers in genetically obese-prone and palatable cafeteria HFD induced obese rats, [27][28][29] which may be because of the relatively immature developmental state of rodents at birth. Newborn humans with either high or low leptin levels at birth have a higher risk of developing obesity and type 2 diabetes compared with those who have normal leptin levels.…”

Section: Discussionmentioning

confidence: 99%

Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth

2008

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Objective: Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth. Design: Female Sprague-Dawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups. Measurements: Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR. Results: Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53±0.13 vs 1.05±0.21 ng ml À1 ; female: 0.33 ± 0.09 vs 2.12 ± 0.57 ng ml À1 , respectively; both Po0.05). Hypothalamic mRNA expression of NPY, pro-opiomelanocortin, leptin receptor and STAT3 were also significantly lower in pups from obese dams. Conclusion: Long-term maternal obesity, together with lower leptin levels in pups from obese dams may contribute to the lower expression of key appetite regulators on day 1 of life, suggesting altered intrauterine neuron development in response to intrauterine overnutrition, which may contribute to eating disorders later in life.

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Diet-induced obesity in gravid rats engenders early hyperadiposity in the offspring

Cited by 48 publications

References 36 publications

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth

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