FETAL PROGRAMMING AND OBESITY SARAH OSSLER SARAH OSSLERCCHMC

FETAL PROGRAMMING AND OBESITY SARAH OSSLER SARAH. OSSLER@CCHMC. ORG

LEARNING OBJECTIVES • To understand multifactorial disease factors • To be able to explain the Barker hypothesis • Understand why methylation is a possible mechanism for the Barker hypothesis • Demonstrate knowledge of environmental factors on adult disease through completion of activity

OBESITY • What is Obesity? • An excess accumulation of fat • A disease that affects nearly one-third of the adult American population (approximately 60 million). • Each year, causes at least 300, 000 excess deaths and healthcare costs of approximately $100 billion in the U. S.

BMI • Body Mass Index (BMI) is a measurement tool used to determine excess body weight • Normal is a BMI less than 25 • Overweight is a BMI of 25 or more • Obesity is a BMI of 30 or more • Morbid obesity is a BMI of 40 or more

NATURE VS. NURTURE • Do your genes impact factors on outcome, or does your environment impact factors on outcome? • BOTH! • Most adult conditions are multifactorial • Obesity • Type 2 Diabetes • Atherosclerotic heart disease

MULTIFACTORIAL INHERITANCE

QUIZ • Name some factors that may influence a persons risk for developing obesity

FETAL PROGRAMMING • The environment a fetus is in can affect disease status later in life • • Malnutrition Disease of mother Drug intake Etc.

OBESITY AND FETAL PROGRAMMING • Early influences can affect a persons weight later in life • Children of gestational diabetic mothers are more likely to be obese • Children of obese mothers are more likely to be obese • Obesity of normal chow diet mice increase when mother has diet induced obesity

BARKER HYPOTHESIS • The thrifty phenotype hypothesis • Hypothesized that poor fetal and early post-natal nutrition sets in motion mechanisms of nutritional thrift • Unknown mechanism of action (Hales CN, Barker DJ, 1992)

METHYLATION • Methylation Is a Plausible Mechanism For the Barker Hypothesis • Additional support includes methylation at IGF 2 • Associated with newborn anthropometrics (St-Pierre et al. Epigenetics 2012) • Associated with overweight at 1 year of age (Perkins et al. J Peds, 2012) • IGF 2 methylation responsive to prenatal diet (Claycombe et al. J Nutr, 2013) • Individuals exposed to famine prenatally demonstrate persistent changes 6 decades later (Heijmans et al. PNAS, 2008)

METHYLATION • Can help control gene expression • Unmethylated DNA free to be transcribed • Methylation can silence expression • Most Cp. G sites across the genome are methylated most of the time • Cp. G-rich regions (Cp. G islands) generally unmethylated • Methylation in these areas can silence genes

METHYLATION • The Agouti mouse model demonstrates how methylation can influence obesity

FOLATE • Folate carries a methyl group • Dietary folate can increase methylation • Dietary folate in agouti mice can rescue the phenotype

PAIR/SHARE • Please turn to the person next to you and explain why methylation is a plausible mechanism for the Barker hypothesis • 1 minute • Please ask questions if they arise!

GENETIC ASPECTS

GENETIC ASPECTS • Identical twin studies can be performed to understand environmental factors • Genetics are identical (generally) • Can focus on environment

ENVIRONMENTAL FACTORS • Food Consumption • In roughly the quarter century* from the 1970 s to the 1990 s: • daily energy intake for teens increased by about 200 kilocalories • intake of sweetened sodas roughly tripled • milk intake dropped by about one third • breakfasts increasingly skipped as a meal • “fast food outlets” increased in use

CONCLUSIONS • Fetal development environment can play a critical role in adult disease • The Barker hypothesis was the first to describe thrifty phenotype • Methylation is a plausible mechanism for the Barker hypothesis • Obesity and other adult onset conditions are multifactorial conditions

ACTIVITY • Count the calories that you consume on an average day

QUESTIONS?