Not all people who are obese demonstrate symptoms commonly associated with being excessively fat; in fact, those who are overweight yet show no signs of insulin resistance, high cholesterol, or high blood pressure comprise about 10 to 40 percent of all obese individuals. Having conducted a new study of this condition, researchers from the University of Helsinki have concluded that such ‘metabolically healthy obesity’ is linked to both a lack of inflammation and the maintenance of healthy mitochondrial function in cells.

Unlike most studies, though, it was not the hypothesis or conclusion that offered the biggest surprise — it was the study's unusual design.

“We used a rare … obesity-discordant [identical] twin-pair design, which uniquely enables the control for genetic background, early development and environment, age and sex between obese and lean individuals,” wrote the authors in their recent paper.

Identical Twin Sets

The authors found 16 pairs of identical twins who were ‘discordant’ in terms of weight: one obese, the other light. Then, they added to their study 11 pairs of ‘concordant’ twins for comparison purposes and also to provide a wide distribution of differences in body mass index (BMI) and weight. All of the twins, both weight-concordant and weight-discordant, were Finnish and between the ages of 22 and 36. The researchers, then, gathered information from them all.

In all 16 pairs, the average weight difference between the obese twin and the lean twin was about 38 lbs. In half of these pairs, the obese co-twins were considered to be metabolically unhealthy: they were found to have significantly higher liver fat (around seven times higher), a 78 percent increase in insulin production during an oral glucose tolerance test, increased CRP (C-reactive protein increases with inflammation), significantly more disturbance in the blood fat profile, and greater tendency for high blood pressure in comparison to their lean twins. Meanwhile, in the other eight pairs, the obese co-twin did not differ from the non-obese co-twin in liver fat, insulin sensitivity, CRP, lipids, blood pressure, or metabolic characteristics of subcutaneous adipose tissue (fat just below the surface of the skin). In other words, these heavier twins demonstrated 'metabolically healthy obesity.' They were the health equal of their leaner co-twins.

To understand why some heavy people remained healthy while others did not, the researchers shifted their focus to studying only the overweight twins minus their lean twins.

Underlying Factors

What the researchers found when comparing the unhealthily obese twins to the metabolically healthy obesity (MHO) twins was that the expression of mitochondrial oxidative phosphorylation in the subcutaneous adipose tissue seemed to be down-regulated — the cells within the fat just below the surface of the skin did not metabolize fat as efficiently as in the MHO twins. And chronic inflammation was up-regulated in the unhealthily fat twins as well. Both of these signs are problems that could lead to complications and disease, including diabetes.

"Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO," the authors concluded. Although they hypothesized that the metabolically healthy obesity twins may begin to develop complications over time and with advancing age, the fact remains for now at least that they demonstrate health equal to their leaner twins.

“Future studies of the MHO phenotype may suggest new potentially drug targets — with the most effective intervention point perhaps being improving mitochondrial function and prevention of inflammation in adipose tissue,” the authors wrote.

 

Source: Naukkarinen J, Heinonen S, Hakkarainen A, et al. Characterising metabolically healthy obesity in weight-discordant monozygotic twins. Diabetologia. 2013.