1. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 1 Learning objectives

2. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 2 Figure 4.1 Effect of socioeconomic status on birth weight in humans. Social class I- professionals, class II- clerical workers, class III- skilled manual or nonmanual workers, class IV- unskilled workers, class V- unemployed.

3. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 3 Figure 4.2 Influences upon fetal growth. The growth trajectory of the fetus is determined by the genotype. Genetically determined growth rates may be constrained by influences from the mother or placenta. These can act directly on the fetal tissues, for example, maternal hormones crossing the placenta, or indirectly by modifying the range or concentration of nutrients reaching the fetal tissues.

4. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 4 Figure 4.3 The Developmental Origins of Health and Disease hypothesis. Maternal Undernutrition promotes fetal undernutrition, which in turn will slow fetal growth rates. The relationship between fetal undernutrition and disease in later life may be directly the result of fetal adaptations to undernutrition, or may be related to the restriction of fetal growth and organ development.

5. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 5 Figure 4.4 Global protein availability statistics. Data extracted from 2004 FAO Food balance sheets. Food balance methods only determine the protein available (i.e., produced through agriculture or imported) per head of population. Actual consumption will be below the figures shown and highly variable within each region (e.g., affluent versus poor, urban versus rural). Sixty-five percent of the world population are likely to consume protein at less than the UK Reference Nutrient Intake, and are therefore at risk of low protein intake during pregnancy. Many in developing countries rely on lower quality plant protein sources.

6. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 6 Figure 4.5 The thrifty phenotype hypothesis. (Source: Adapted from Hales and Barker (2001).)

7. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 7 Research Highlight 4 Thrifty phenotype or thrifty genotype?

8. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 8 Figure 4.6 The principle of tissue remodeling. During embryonic and fetal life, progenitor cells undergo rounds of proliferative cell division. Following this proliferative phase, the cells undergo differentiation to form diverse cell types that will perform the physiological functions of the mature organ. Adverse environments during either phase will modify the cell numbers or types that appear in the mature organ.

9. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 9 Figure 4.7 Placental 11ß-hydroxysteroid dehydrogenase (11ßHSD2) acts as a barrier to the movement of active glucocorticoids between mother and fetus. (a) Normal gatekeeper functions of 11ßHSD2 convert active cortisol to inactive cortisone and hence protect fetal tissues from hormones of maternal origin. Only synthetic glucocorticoids such as dexamethasone may pass across the placenta unchanged. (b) In the undernourished mother, expression of 11ßHSD2 in placenta is diminished and hence the fetal tissues are overexposed to active glucocorticoids.

10. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 10 Figure 4.8 Programming of hepatic lipid metabolism by a maternal low-protein diet in the rat. Pregnant rats were fed a low-protein diet throughout pregnancy. (a) At 18 months of age their offspring showed histological evidence of hepatic steatosis (arrow shows white lipid deposits within the liver tissue). (b) The mRNA expression of fatty acid synthase, a key enzyme in the synthesis of lipid was suppressed in the low protein exposed offspring at 1 month of age, but (c) was elevated in the older animals. (Source: Data from Erhuma et al. (2007).)

11. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 11 Figure 4.9 DNA methylation and histone acetylation are epigenetic mechanisms that regulate gene transcription. CpG islands in DNA may be methylated or unmethylated. In the unmethylated state, the histone proteins associated with the DNA tend to be acetylated and the DNA is less tightly coiled. Transcription factors and transcription machinery can access gene promoters and hence the Unmethylated genes can be expressed. Methylation leads to deacetylation of histones and prevents transcription.

12. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 12 Figure 4.10 Postnatal treatment with antihypertensive drugs reverse programming effects of maternal undernutrition. Pregnant rats were fed control or low-protein (LP) diets in pregnancy. On giving birth all animals were fed the same diet, but half of the litters from each group were treated with losartan, an antagonist of the angiotensin II AT1 receptor for 2 weeks. Blood pressure was measured 8 weeks later. Blood pressure of offspring from untreated LP-fed rats was elevated compared to controls, but the LP-exposed rats treated with losartan had normal blood pressure. (Source: Data from Sherman and Langley-Evans (2000).)

13. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 13 Figure 4.11 Programming of blood pressure across generations. Pregnant rats were fed control or low-protein (LP) diets in pregnancy. On giving birth, all animals were fed the same diet and when adult the offspring were mated to produce four separate crosses (control male x control female, control male x LP female, LP male x control female, LP male x LP female). Blood pressures of first-generation and second-generation offspring were measured at 8 weeks of age. F1: first generation. F2: second generation. (Source: Data from Harrison and Langley-Evans (2009).)

14. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 14 Summary Box 4

15. Nutrition: A Lifespan Approach, by Simon Langley-Evans. © 2009 Simon Langley-Evans. 15 Self-Assessment Questions