The term “healthy obesity” has gained traction over the past 15 years, but scientists have recently questioned its very existence.
A study published in Cell Reports provides further evidence against the notion of a healthy obese state.
It reveals 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 findings suggest that vigorous health interventions may be necessary for all obese individuals, even those previously considered to be metabolically healthy.
Since obesity is the major driver altering gene expression in fat tissue, people should continue to focus on preventing obesity.
Obesity has reached epidemic proportions globally, affecting approximately 600 million people worldwide and significantly increasing the risk of heart disease, stroke, cancer, and type 2 diabetes.
Since the 1940s, evidence supporting the link between obesity and metabolic and cardiovascular diseases has been steadily growing.
But in the 1970s and 80s, experts began to question the extent to which obesity increases the risk for these disorders.
Subsequent studies in the late 90s and early 2000s showed that some obese individuals display a relatively healthy metabolic and cardiovascular profile.
Recent estimates suggest that up to 30% of obese individuals are metabolically healthy and therefore may need less vigorous interventions to prevent obesity-related complications.
A hallmark of metabolically healthy obesity is high sensitivity to the hormone insulin, which promotes the uptake of blood glucose into cells to be used for energy.
However, there are currently no accepted criteria for identifying metabolically healthy obesity, and whether or not such a thing exists is now up for debate.
To address this controversy, researchers assessed responses to insulin in 15 healthy, never-obese participants and 50 obese people enrolled in a clinical study of gastric bypass surgery.
The researchers 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 influenced by cardiovascular or metabolic risk factors such as waist-to-hip ratio, heart rate, or blood pressure.
The findings showed that obesity rather than other common risk factors is likely the primary factor determining metabolic health.
Researchers suggest that the notion of metabolically healthy obesity may be more complicated than previously thought. There doesn’t appear to be a clear sign that differentiates obese subjects with high or low insulin sensitivity.
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.
Moreover, all of the obese people were scheduled to undergo bariatric surgery, so the findings may only apply to individuals with severe obesity.
In future research, researchers will track the study participants after bariatric surgery to determine whether weight loss normalizes gene expression responses to insulin.
They will also look for specific genes linked to improved metabolic health in these individuals.
Citation: Rydén M, et al. (2016). The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity. Cell Reports, 16: 2317-2326. DOI: http://dx.doi.org/10.1016/j.celrep.2016.07.070.
Figure legend: This Knowridge.com image is credited to Ryden et al./Cell Reports 2016.