Lifestyle can alter gene activity, lead to insulin resistance

June 19, 2008

BETHESDA, Md. (June 18, 2008) A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy. The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.

The study, "Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity," appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism, published by The American Physiological Society (www.the-aps.org).

The study was carried out by Linda Mustelin and Kirsi Pietiläinen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi Sovijärvi and Päivi Piirilä of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-Järvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.

Environment can influence genes

Recent studies have suggested that defects in expression of genes involved in the body's conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.

Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.

The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.

Among the discordant pairs, the study found the obese twin had significantly lower:Heredity may still play role

"These data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects," the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.

"Although we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism," lead author Linda Mustelin noted.

The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.
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NOTE TO EDITORS: To interview one of the researchers, please contact Christine Guilfoy at (301) 634-7253 or at cguilfoy@the-aps.org.

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (www.The-APS.org/press) has been an integral part of this discovery process since it was established in 1887.

American Physiological Society

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