We determined the effects of maternal diet-induced obesity on offspring adipose tissue insulin signalling and miRNA expression in the aetiology of insulin resistance in later life. Although body composition and glucose tolerance of 8-week-old male offspring of obese dams were not dysregulated, serum insulin was significantly (p<0.05) elevated. Key insulin signalling proteins in adipose tissue were down-regulated, including the insulin receptor, catalytic (p110β) and regulatory (p85α) subunits of PI3K as well as AKT1 and 2 (all p<0.05). The largest reduction observed was in IRS-1 protein (p<0.001), which was regulated post-transcriptionally. Concurrently, miR-126, which targets IRS-1, was up-regulated (p<0.05). These two features were maintained in isolated primary pre-adipocytes and differentiated adipocytes in-vitro. We have therefore established that maternal diet-induced obesity programs adipose tissue insulin resistance. We hypothesise that maintenance of the phenotype in-vitro strongly suggests that this mechanism is cell autonomous and may drive insulin resistance in later life.

Although iron deficiency is the most common single-nutrient deficiency in infants and children, other deficiencies may develop concurrently, including zinc deficiency. In previous studies, we used home-fortification with "Sprinkles," single-serve sachets containing microencapsulated ferrous fumarate added to weaning foods, to successfully treat anemia. This mode of micronutrient delivery is amenable to the delivery of other micronutrients. However, the relative efficacy of multiple micronutrient supplements for the treatment of anemia requires evaluation due to possible nutrient interactions. Thus, we evaluated the relative efficacy of Sprinkles formulated with iron and zinc in anemic infants, compared with Sprinkles formulated with iron alone. We studied 304 anemic infants (mean age 10.3 +/- 2.5 mo; hemoglobin 87.4 +/- 8.4 g/L) in rural Ghana. A combined supplementation group (FeZn) received daily Sprinkles containing 80 mg iron and 10 mg zinc; a comparison group (Fe) received Sprinkles (80 mg iron) without zinc for 2 mo. The rate of recovery from anemia was higher in the Fe group compared with the FeZn group (74.8 vs. 62.9%; P = 0.048). The plasma zinc concentration decreased significantly in both groups (P < 0.05). A significant decline in the height for age Z-score was observed in the FeZn group (P = 0.0011), but there was no change in the Fe group. These results suggest that in a controlled setting, home-fortification using micronutrient Sprinkles with iron, or iron and zinc, was very successful in treating anemia; however, this intervention alone was insufficient to improve zinc status or promote catch-up growth in this stunted and wasted population.