Nutrigenomics Nutrigenetics and Obesogenic Environment Safarina G Malik

Nutrigenomics, Nutrigenetics and Obesogenic Environment Safarina G. Malik ina@eijkman. go. id 08/11/2017 Lembaga Biologi Molekuler Eijkman Jl Diponegoro 69, Jakarta 10430 Indonesia 1

Nutritional Genomics 08/11/2017 Stover, PJ. Physiol Genomics, 2004 2

Obesity is correlated with energy imbalance • High food intake § Global shift in eating habits § Access to processed food § High sugar, fat and calories § Less nutrients § Reduced intake of vitamins and minerals • Low physical activity § Too little or no exercise § More leisure-time physical activity § Increase in sedentariness 08/11/2017 3

Obesity, Genetics and Environment Genetic factors Obesogenic environment • Macronutrient composition and nutrient partitioning • Gene polymorphisms on the response of body weight • Weight-related phenotypes and relative success of weight-loss programs that include nutritional interventions • Increased food intake (fast food restaurants, grocery store locations) • Decreased physical activity (cul-de-sac neighbourhoods, limited opportunities) 08/11/2017 4

Genetics and Obesogenic Environment The obesogenicity of an environment has been defined as 'the sum of influences that the surroundings, opportunities, or conditions of life have on promoting obesity in individuals or populations‘ (Lake and Townshend, J R Soc Promot Health 2006) Balagopal P, Pediatr Ann 2006 08/11/2017 5

The Inuit of Greenland Survived for generations eating almost nothing but meat in a landscape too harsh for most plants Ann Gibbons – Nat Geo 16/11/2017 Their FADS region has been under selection, driven by a diet high in PUFAs Fumagalli et al, Science 2015 6

Lifestyle modifies obesity-associated risk of cardiovascular disease in a genetically homogeneous population of Inuit Jørgensen et al, Am J Clin Nutr 2006 Systolic blood pressure by BMI category of BMI in Inuit residents from Greenland Inuit migrants from Denmark Diastolic blood pressure by BMI category of BMI in Inuit residents from Greenland Inuit migrants from Denmark migrants (n=995); residents of Greenland (n=1316); dotted line, Danes (reference; n=784) 08/11/2017 7

Obesity prevalence is increasing in Indonesia Male Female Riskesdas Data 08/11/2017 8

Diverse influences on the epidemic lifestyle disease – what to do and how? Host Factors (Genetic background, immunological state) The problem: An epidemic of obesity driven by lifestyle change. Human Health Socio-economic, environment (in-utero exposure, diet, pharmaceuticals, exercise) Gut Microbiota (composition, activity) Greater understanding of the tripartite influence of on the host state is needed IMELDA: Indonesian Model for Epidemic Lifestyle Disease Associations 9 08/11/2017

The IMELDA Project: Linking genetic diversity, gut microbiota and lifestyle-disease North Kalimantan 40 samples: All females, Age 18 – 27 Biometrics (incl. BMI) Bali Diet Data Fecal Microbiota West Sumba Mt. Kidul Febinia CA et al, manuscript in prep 16/11/2017 10

Mt. DNA genetic background is associated with waist-hip biometrics Mt. DNA macro-haplogroup M: higher WC and WHR 16/11/2017 Febinia CA et al, manuscript in prep 11

Protein Intake Ratio in Bali is Associated with Obesity Diet differences by obesity lean obese vs. lean Diet Components (n = 38) (n = 8) p-value % kcal Carbohydrate 51 ± 11 53 ± 13 0. 692 % kcal Fat 30 ± 11 32 ± 13 0. 723 % kcal Protein 19 ± 5 15 ± 3 0. 035 31/10/2017 Febinia CA et al, manuscript in prep 12

Mitochondrial Function and Biogenesis • Power plant of the cell ~ essential for cell viability and survival • Energy production: produce ATP • mt. DNA encodes essential proteins • mt. DNA copy number is modulated by stressors Wallace, Annu Rev Genet 2005 08/11/2017 13

Mitochondrial medicine: Defiency and sufficiency of mitochondrial nutrient 08/11/2017 Chowanadisai et al, 2011 14

SUMMARY • Obesity occur due to energy imbalance • Genetics and environment, in particular obesogenic environment, play important role in obesity manifestation • Defiency and sufficiency of mitochondrial nutrient determine overall mitochondrial performance • Balinese’ mt. DNA haplogroups is associated with WC and WHR • Obese Balinese have less protein intake than their lean counterpart 16/11/2017 15

Acknowledgement Eijkman Institute for Molecular Biology § Hidayat Trimarsanto § Clarissa A. Febinia § Sukma Oktavianthi § Herawati Sudoyo § Lidwina Priliani, MSc § Ria Hasnita § Artricia Rasyid § Rut C. Inggriani § Asri Sulfianti § Rahma Fitri Hayati Charles Perkins Centre, the University of Sydney § Andrew Holmes 08/11/2017 Faculty of Medicine, Udayana University § Ketut Suastika § Made Ratna Saraswati § I Wayan Weta § Desak Made Wihandani § Pande Dwipayana § Students of Faculty of Medicine Faculty of Public Health, Universitas Indonesia § Ratna Djuwita Hatma § Rizka Maulida 16

Thank you Gene hunter @ Eijkman Institute 08/11/2017 17