Impact of Metabolic Hormones Secreted in Human Breast Milk on Nutritional Programming in Childhood Obesity

The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.

One third of the Indian babies are of low birth weight (<2.5 kg), and this is attributed to maternal undernutrition. We therefore examined the relationship between maternal nutrition and birth size in a prospective study of 797 rural Indian women, focusing on macronutrient intakes, dietary quality and micronutrient status. Maternal intakes (24-h recall and food frequency questionnaire) and erythrocyte folate, serum ferritin and vitamin C concentrations were measured at 18 +/- 2 and 28 +/- 2 wk gestation. Mothers were short (151.9 +/- 5.1 cm) and underweight (41.7 +/- 5.1 kg) and had low energy and protein intakes at 18 wk (7.4 +/- 2.1 MJ and 45.4 +/- 14.1 g) and 28 wk (7.0 +/- 2.0 MJ and 43.5 +/- 13.5 g) of gestation. Mean birth weight and length of term babies were also low (2665 +/- 358 g and 47.8 +/- 2.0 cm, respectively). Energy and protein intakes were not associated with birth size, but higher fat intake at wk 18 was associated with neonatal length (P < 0.001), birth weight (P < 0.05) and triceps skinfold thickness (P < 0.05) when adjusted for sex, parity and gestation. However, birth size was strongly associated with the consumption of milk at wk 18 (P < 0.05) and of green leafy vegetables (P < 0.001) and fruits (P < 0.01) at wk 28 of gestation even after adjustment for potentially confounding variables. Erythrocyte folate at 28 wk gestation was positively associated with birth weight (P < 0.001). The lack of association between size at birth and maternal energy and protein intake but strong associations with folate status and with intakes of foods rich in micronutrients suggest that micronutrients may be important limiting factors for fetal growth in this undernourished community.

Metabolic disorders have seen an increased prevalence in recent years in developed as well as developing countries. While it is clear lifestyle choices and habits have contributed to this epidemic, mounting evidence suggests the nutritional milieu during critical stages of development in early life can “program” individuals to develop the metabolic syndrome later in life. Extensive epidemiological data presents an association between maternal obesity and nutrition during pregnancy and offspring obesity, and a number of animal models have been established in order to uncover the underlying mechanisms contributing to the programming of physiological systems. It is hard to distinguish the causal factors due to the complex nature of the maternal–fetal relationship; however, in order to develop adequate prevention strategies it is vital to identify which maternal factor(s) – be it the diet, diet-induced obesity or weight gain – and at which time during early development instigate the programmed phenotype. Curtailing the onset of obesity at this early stage in life presents a promising avenue through which to stem the growing epidemic of obesity.