Experts weigh 'healthy' obese claims
Swedish researchers are challenging the idea of ‘healthy obesity’.
Obesity is at epidemic proportions around the world, affecting approximately 600 million people.
Research over decades has showed that obesity significantly increases the risk of heart disease, stroke, cancer, and type 2 diabetes.
But in more recent years, experts have questioned the extent to which obesity increases the risk for these conditions.
Some studies have now suggested that obese individuals can still display a relatively healthy metabolic and cardiovascular profile.
So-called ‘metabolically healthy’ obesity has been characterised by high sensitivity to the hormone insulin, which promotes the uptake of blood glucose into cells to be used for energy.
But new research in the journal Cell Reports provides evidence that the notion of a healthy obese state could be false.
It shows that white fat tissue samples from obese individuals classified as either metabolically healthy or unhealthy actually show nearly identical, abnormal changes in gene expression in response to insulin stimulation.
The study suggests the major indicator of alleged ‘healthy obesity’ may not apply.
“The findings suggest that vigorous health interventions may be necessary for all obese individuals, even those previously considered to be metabolically healthy,” says first author Mikael Rydén of the Karolinska Institutet.
“Since obesity is the major driver altering gene expression in fat tissue, we should continue to focus on preventing obesity.”
The researchers looked at responses to insulin in 15 healthy, never-obese participants and 50 obese subjects enrolled in a clinical study of gastric bypass surgery. They took biopsies of abdominal white fat tissue before and at the end of a two-hour period of intravenous infusion of insulin and glucose.
Based on the glucose uptake rate, the researchers classified 21 obese subjects as insulin sensitive and 29 as insulin resistant.
Surprisingly, mRNA sequencing of white fat tissue samples revealed a clear distinction between never-obese participants and both groups of obese individuals.
White fat tissue from insulin-sensitive and insulin-resistant obese individuals showed nearly identical patterns of gene expression in response to insulin stimulation. These abnormal gene expression patterns were not linked to cardiovascular or metabolic risk factors such as waist-to-hip ratio, heart rate, or blood pressure.
The findings suggest that obesity is the primary factor determining metabolic health.
“Our study suggests that the notion of metabolically healthy obesity may be more complicated than previously thought, at least in subcutaneous adipose tissue,” Rydén says.
“There doesn't appear to be a clear transcriptomic fingerprint that differentiates obese subjects with high or low insulin sensitivity, indicating that obesity per se is the major driver explaining the changes in gene expression.”
One limitation of the study is that it examined gene expression profiles only in subcutaneous white fat tissue, not other types of fat tissue or other organs. Additionally, all of the obese subjects were scheduled to undergo bariatric surgery, so the findings may only apply to individuals with severe obesity.
A follow-up study has already started to track the same patients after bariatric surgery to see how their weight loss might change their gene expression responses to insulin, while also looking for specific genes linked to improved metabolic health in these individuals.