2005

J Nutr. 2005 Jun;135(6):1382-6.
Dietary protein restriction of pregnant rats induces and folic Acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring.
Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC.
Development and Cell Biology.

Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression. We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group). Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPARalpha gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups. The RF diet prevented these changes. PPARgamma methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPARalpha. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming.

2000

Endocr J 2000 Dec;47(6):787-91.
A case of obesity, diabetes and hypertension treated with very low calorie diet (VLCD) followed by successful pregnancy with intrauterine insemination (IUI).
Katsuki A, Sumida Y, Ito K, Murashima S, Gabazza EC, Furuta M, Yano Y, Sugiyama T, Toyoda N, Adachi Y.
Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.

The patient was a 32-year-old obese woman with a history of type 2 diabetes and hypertension for 6 years. Although she was treated with antihypertensive agents and intensive insulin therapy, her hyperglycemia was difficult to control. She wanted to have a baby but pregnancy was not recommended because her diabetes was under poor control and the use of antihypertensive medication. To achieve good control of obesity, diabetes and hypertension, she was admitted to our clinical department for weight reduction using very low calorie diet (VLCD). During VLCD she had a 19.8 kg reduction in body weight and her blood glucose and blood pressure were in good control without the use of drugs. Five months later, she became pregnant after the fourth trial of intrauterine insemination (IUI) and gave birth to a female baby under insulin therapy. This is the first report that showed the usefulness of VLCD for prepregnant control of glucose metabolism and blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

1987

Neurobiol Aging 1987 May-Jun;8(3):225-32.
Rejuvenating effects of 10-week underfeeding period on estrous cycles in young and old rats.
Quigley K; Goya R; Meites J.

The effects of providing 50% of normal feed intake for 10 weeks followed by 16 weeks of ad lib feeding on estrous cycles and mammary tumor incidence were studied in female rats initially 4 months and 15-16 months old. Initially all young rats exhibited regular or irregular estrous cycles and only about 41% of the older rats cycled regularly or irregularly; the remainder of the older rats did not cycle. During underfeeding, both the young and older rats lost body weight and ceased to cycle. After refeeding 100% of both young and old rats resumed cycling, the young rats for a much longer period than the old rats, and more of both groups continued to cycle than their ad lib-fed controls. Upon refeeding, the young and old rats reached the body weights of the ad lib-fed controls in about 3 weeks. Mammary tumors were initially present only in old rats and regressed during underfeeding; they rapidly reached control size upon refeeding. Plasma PRL levels declined during underfeeding but rebounded to higher than control values upon refeeding in both young and old rats. In young but not in old rats, plasma LH levels fell during underfeeding but returned to control values upon refeeding. These results demonstrate that a relatively short period of underfeeding, followed by refeeding, can delay the decline in reproductive cycles in young rats and reinitiate estrous cycles in older rats. These effects appear to be mediated via the neuroendocrine system.