Lifestyle More Than Heredity Leads to Insulin Resistance in Obese People

In a study of identical twins, Finnish researchers have found that lifestyle contributes more than heredity in altering gene activity, which in turn can lead to insulin resistance

In a study of identical twins, Finnish researchers have found that lifestyle contributes more than heredity in altering gene activity, which in turn can lead to insulin resistance in people who are obese.

While Insulin resistance is known to increase the chance of developing diabetes and heart disease, the study suggests that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy.

With recent studies suggesting 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.

And they reasoned it by saying that as the twins in the study were identical, any differences that were found could be attributed to environmental factors.

The study was carried out on 24 pairs of identical twins, born in Finland between 1975 and 1979. Of these 14 pairs (8 male and 6 female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of 5 male and 5 female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.

For the study, their whole body insulin sensitivity, body composition and cardiorespiratory fitness were measured. A needle biopsy of abdominal subcutaneous fat tissue was also obtained, although they were unable to obtain this measurement for one of the discordant pairs.

The study found that among the discordant pairs, the obese twin had significantly lower insulin sensitivity, which suggested that the body has a harder time using glucose to produce energy. Also, they also scored lower in fitness levels, as measured by maximum oxygen uptake and maximum work capacity.

Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation) was also found to be lower in the obese twin. Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.

"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," wrote the authors.

They also pointed out 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," said lead author Linda Mustelin.

The researchers are now planning to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.

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.

Source-ANI
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