The Interplay of Genes and Diet in Metabolic Diseases and Aging: Studies on Obesity, Osteoporosis and Survival

Obesity and osteoporosis are common and complex disorders with important consequences for human health and for society. The two conditions are intimately linked, as evidenced by epidemiological studies showing that obesity protects from osteoporosis while low body weight poses a strong risk factor 1, 2. Obesity, defined as a body mass index (BMI) of 30 kg/m2 and over, has become a global epidemic and represents an important risk factor for type 2 diabetes mellitus, hypertension, cardiovascular disease, stroke, some types of cancer and disability. Osteoporosis, a skeletal disorder characterized by loss of bone strength and proneness to fractures, is a major health threat to hundreds of millions of elderly individuals worldwide and prevalence will continue to rise as populations age. Osteoporosis and obesity result from an interaction between genetic factors and environment. Although the growing prevalence of obesity is most likely driven by changing lifestyles encompassing increased caloric intake and decreased energy expenditure through physical activity, individual susceptibility varies widely and is strongly influenced by genetic factors. Heritability estimates for BMI, the most widely used parameter of obesity, range from 30 to 70% in family- and twin studies 3. There are also genetic influences on obesity-related traits like total body fat mass, lean mass and measures of fat distribution 4-8, but the heritability of these parameters is less clear than that of BMI. A large contribution of genes has also been documented for the susceptibly to develop osteoporosis. Heritability estimates for bone mineral density (BMD), the most widely used parameter for osteoporosis, range between 50 and 85% 9. The age-adjusted heritability of osteoporotic fractures is smaller (between 25 and 50%) and may be independent to that of BMD 10, possibly due to other important factors associated with fractures such as falls.

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