An estimated one-quarter of individuals who are obese are metabolically healthy and do not have a high risk of developing type 2 diabetes, and a study published by Cell Press aims to provide a possible explanation. Obesity is a significant risk factor for diabetes, though the two conditions are not always linked. The research study reveals that high levels of a molecule called heme oxygenase-1 (HO-1) are linked to poor metabolic health and increased risk of type 2 diabetes in obese persons, but an inhibition of HO-1 improved metabolic health in obese mice.

The improvement in metabolic health suggests that HO-1 blockers could represent a new strategy for the treatment of metabolic disease. The researchers found higher levels of HO-1 in liver and fat biopsies from obese, insulin-resistant humans compared with obese, metabolically healthy individuals, according to a Science Daily news report. When the HO-1 gene in immune cells called macrophages was deleted, molecular signs of inflammation decreased in mice, which suggests that HO-1 may promote inflammation.

In addition, the deletion of the HO-1 gene specifically in the liver or macrophages of mice fed a high-fat diet led to better liver function and an increase in insulin sensitivity, which is a clear sign of improved metabolic health, as noted in the Science Daily news release.

Harald Esterbauer, MD, PhD, senior author of the study, states, “The results indicate that HO-1 is in fact necessary for the development of metabolic disease and call for a re-evaluation of numerous findings in the field. The study also reveals HO-1 as a candidate biomarker for the stratification of metabolically healthy and unhealthy obesity and provides a framework for selective, personalized therapy.”

J. Andrew Pospisilik, PhD, a co-researcher on the project, says, “Our findings show that HO-1 is among the strongest predictors of metabolically unhealthy obesity in humans, and it could have a high prognostic value for detecting disease onset. This could allow clinicians to use targeted interventions to prevent disease progression specifically in obese individuals who show early signs of type 2 diabetes.”

[Sources: Science Daily, Cell Press]