Twin study on the increased cardiometabolic risk in obesity

A unique monozygotic twin study by researchers from the Finnish Twin Cohort, Helsinki University Central Hospital, and VTT Technical Research Centre of Finland found that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.

By studying monozygotic twins discordant for obesity the research group was able to eliminate effects caused by genetic differences related to obesity and reveal effects attributable to environmental and life-style differences.

Obesity and its many related health hazards have become a serious and growing problem worldwide. While environmental and lifestyle factors play a key role in the development of obesity, genetic variation may determine an individual's susceptibility to weight gain and to the rise of obesity-related health risks. Obesity increases the risk of cardiovascular diseases and diabetes especially when the extra fat is accumulated to central and intra-abdominal depots and when obesity is accompanied by an atherogenic dyslipidemia.

A Finnish team from the Finnish Twin Cohort, Helsinki University Central Hospital, and VTT Technical Research Centre of Finland performed a metabolomic analysis of lipids in 14 monozygous twins highly discordant for obesity, and 10 control pairs concordant for weight. They found that acquired obesity, independent of genetic influences, primarily relates to increases in lysophosphatidylcholines, constituents of an atherogenic lipid profile and decreases in ether phospholipids, lipids with anti-oxidative properties.

The origin of obesity and related dyslipidemias is multifactorial, involving complex genetic and environmental networks. Not all obese individuals develop dyslipidemia and not all dyslipidemic patients are obese. Cross-sectional studies comparing lipid profiles in obese vs. non-obese humans do not permit unequivocal distinction between genetic versus environmental and life-style effects. This can best be done by studying monozygotic (MZ) twins discordant for obesity. MZ twins are genetically identical at the sequence level and any differences between the co-twins are thus attributable to environmental factors. The co-twin design controls for age, gender, childhood socioeconomic background and other environmental experiences and exposures.

Serum patterns of small molecules such as lipids reflect the homeostasis of the organism. However, classical measurements of lipids in the clinical setting are unable to detect early changes and abnormalities in specific metabolites. Recent advances have made broad screening of metabolites, i.e. metabolomics, feasible, therefore opening new possibilities for discoveries of sensitive biomarkers for different diseases.

The study convincingly demonstrates the sensitivity of the metabolomics platforms since subtle pathophysiological changes were detected well prior to changes in commonly utilized clinical measures. Of special interest and clinical relevance is the finding that the atherogenic lipid profile of the obese co-twins was associated with whole body insulin resistance, something that could not be detected using classical lipid measures only.

This study is published in PLoS ONE, the international, peer-reviewed, open-access, online publication from the Public Library of Science (PLoS).