Epigenetics and In Utero Acquired Predisposition to Metabolic Disease

Epidemiological evidence has shown an association between prenatal malnutrition and a higher risk of developing metabolic disease in adult life. An inadequate intrauterine milieu affects both growth and development, leading to a permanent programming of endocrine and metabolic functions. Programming may be due to the epigenetic modification of genes implicated in the regulation of key metabolic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs). The expression of miRNAs in organs that play a key role in metabolism is influenced by in utero programming, as demonstrated by both experimental and human studies. miRNAs modulate multiple pathways such as insulin signaling, immune responses, adipokine function, lipid metabolism, and food intake. Liver is one of the main target organs of programming, undergoing structural, functional, and epigenetic changes following the exposure to a suboptimal intrauterine environment. The focus of this review is to provide an overview of the effects of exposure to an adverse in utero milieu on epigenome with a focus on the molecular mechanisms involved in liver programming

The Effects of Nutrition on Linear Growth

Linear growth is a complex process and is considered one of the best indicators of children's well-being and health. Genetics, epigenetics and environment (mainly stress and availability of nutrients) are the main regulators of growth. Nutrition exerts its effects on growth throughout the course of life with different, not completely understood mechanisms. Cells have a sophisticated sensing system, which allows growth processes to occur in the presence of an adequate nutrient availability. Most of the nutritional influence on growth is mediated by hormonal signals, in turn sensitive to nutritional cues. Both macro- and micro-nutrients are required for normal growth, as demonstrated by the impairment of growth occurring when their intake is insufficient. Clinical conditions characterized by abnormal nutritional status, including obesity and eating disorders, are associated with alterations of growth pattern, confirming the tight link between growth and nutrition. The precise molecular mechanisms connecting nutrition to linear growth are far from being fully understood and further studies are required. A better understanding of the interplay between nutrients and the endocrine system will allow one to develop more appropriate and effective nutritional interventions for optimizing child growth

Functional Significance and Predictive Value of MicroRNAs in Pediatric Obesity: Tiny Molecules with Huge Impact?

Obesity is a major health concern. While some children develop comorbidities such as insulin resistance and low-grade systemic inflammation upon weight gain, others stay metabolically healthy. There is an urgent need for clinically relevant markers with prognostic value related to disease development and intervention success. MicroRNAs (miRNAs) are established biomarkers for several disease states. Herein, we give a brief overview of miRNA biogenesis and function and the potential role of circulating miRNA in the context of pediatric obesity

Long-acting growth hormone preparations and their use in children with growth hormone deficiency

Background: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency (GHD) and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. Summary: Different technologies to manipulate drug release have been produced allowing weekly, biweekly or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. Key messages: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of un-physiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules and potential novel side-effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently

The Effects of Nutrition on Linear Growth

Linear growth is a complex process and is considered one of the best indicators of children’s well-being and health. Genetics, epigenetics and environment (mainly stress and availability of nutrients) are the main regulators of growth. Nutrition exerts its effects on growth throughout the course of life with different, not completely understood mechanisms. Cells have a sophisticated sensing system, which allows growth processes to occur in the presence of an adequate nutrient availability. Most of the nutritional influence on growth is mediated by hormonal signals, in turn sensitive to nutritional cues. Both macro- and micro-nutrients are required for normal growth, as demonstrated by the impairment of growth occurring when their intake is insufficient. Clinical conditions characterized by abnormal nutritional status, including obesity and eating disorders, are associated with alterations of growth pattern, confirming the tight link between growth and nutrition. The precise molecular mechanisms connecting nutrition to linear growth are far from being fully understood and further studies are required. A better understanding of the interplay between nutrients and the endocrine system will allow one to develop more appropriate and effective nutritional interventions for optimizing child growth