[pronut-hiv] Diabetes: Nutritional Epigenomics of Metabolic Syndrome

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From Diabetes:

Nutritional Epigenomics of Metabolic Syndrome
New Perspective Against the Epidemic

http://www.medscape.com/viewarticle/508054?src=mp

Catherine Gallou-Kabani; Claudine Junien  

Abstract and Introduction
Abstract
Human epidemiological studies and appropriately designed dietary interventions in animal models have provided considerable evidence to suggest that maternal nutritional imbalance and metabolic disturbances, during critical time windows of development, may have a persistent effect on the health of the offspring and may even be transmitted to the next generation. We now need to explain the mechanisms involved in generating such responses. The idea that epigenetic changes associated with chromatin remodeling and regulation of gene expression underlie the developmental programming of metabolic syndrome is gaining acceptance. Epigenetic alterations have been known to be of importance in cancer for ~2 decades. This has made it possible to decipher epigenetic codes and machinery and has led to the development of a new generation of drugs now in clinical trials. Although less conspicuous, epigenetic alterations have also been progressively shown to be relevant to common diseases such as atherosclerosis and type 2 diabetes. Imprinted genes, with their key roles in controlling feto-placental nutrient supply and demand and their epigenetic lability in response to nutrients, may play an important role in adaptation/evolution. The combination of these various lines of research on epigenetic programming processes has highlighted new possibilities for the prevention and treatment of metabolic syndrome.

Introduction
The recent explosion of the worldwide epidemic of metabolic syndromecombining disturbances in glucose and insulin metabolism, excess predominantly abdominally distributed weight, mild dyslipidemia, and hypertension, with the subsequent development of obesity, type 2 diabetes, and cardiovascular diseasecompromises progress made in reducing the morbidity and mortality of cardiovascular disease in recent years.[1] In the last 10 years, a series of studies, notably those by Hales and Barker,[2] who first coined the term "fetal programming" leading to a "thrifty phenotype," have demonstrated that these common disorders take root in early nutrition, during gestation and lactation.

A significant and increasing proportion of women (14-27%) are overweight when pregnant. Whereas the long-term effects of gestational diabetes are well documented,[3,4] the consequences of metabolic syndrome in the mother, together with an unbalanced diet and metabolic disturbances during the periconceptual period, gestation, and lactation, for fetal programming, for the various critical windows of development, and during aging[5] are poorly documented and remain to be explored.[6]

A recent review examined animal studies in which the fetal and postnatal environment had been manipulated by changing maternal dietary intake or modifying uterine artery flow.[6] Most studies examined the consequences of protein restriction during gestation, conditions not fully matching the features of the current epidemic of metabolic syndrome. Fewer studies have dealt with the consequences of a high-carbohydrate or fat-rich diet, conditions corresponding more closely to the current epidemic of metabolic syndrome. However, it remains unclear whether metabolic syndrome can be reliably induced by the interventions made because of differences between protocols, diets (e.g., type of fatty acids), sex, and time periods examined.[6]

Recent experiments have shown that the features of metabolic syndrome in the adult offspring of fat-fed rats may be acquired antenatally and during suckling. Moreover, exposure during pregnancy confers adaptive protection against endothelial dysfunction, but not against hypertension, because of maternal fat feeding during suckling.[7] However, these data only partially reflect the features of metabolic syndrome because pregnant mothers were not overweight and therefore did not display the metabolic disturbances of metabolic syndrome that could also interfere with fetal/postnatal programming. Malnourished fetuses adopt several strategies to optimize their chances of survival during the neonatal period, but these strategies assume that the same type of nutritional conditions will prevail. A selective distribution of nutrients ensures that brain growth is given priority over the growth of other organs, such as the liver, muscle, and pancreas. The adaptations adopted during fetal programming may prove to be detrimental if food becomes more abundant.[8] Thus, any change in conditions may have deleterious consequences.

Catherine Gallou-Kabani, and Claudine Junien, Institut National de la Sant* et de la Recherche M*dicale (INSERM) Unit 383, Clinique Maurice Lamy, H*pital Necker-Enfants Malades, Paris, France

Diabetes.  2005;54(7):1899-1906.  )2005 American Diabetes Association, Inc.