Insulin-Sensitive Obese Individuals may Not be as Healthy as Previously Believed

Obesity has globally emerged as an epidemic affecting over 600 million people worldwide and significantly escalating the risk of heart disease, stroke, cancer, and type two diabetes. A recent estimate suggests 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.

The term 'healthy obesity' that has gained traction over the past 15 years may just be a notion, suggested a new study. The findings revealed 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, we should continue to focus on preventing obesity," said Mikael Ryden, the author of the study.

Reacting to the controversy, Ryden, Carsten Daub, and Peter Arner of the Karolinska Institute assessed responses to insulin in 15 healthy, never-obese participants and 50 obese subjects 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 show that obesity rather than other common risk factors is likely the primary factor determining metabolic health.

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"Our study suggests that the notion of metabolically healthy obesity may be more complicated than previously thought, at least in subcutaneous adipose tissue. 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," Ryden says.

The study has an important take-home message. "Insulin-sensitive obese individuals may not be as metabolically healthy as previously believed," Ryden says. "Therefore, more vigorous interventions may be necessary in these individuals to prevent cardiovascular and metabolic complications." It was published in Cell Reports journal.

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Source-ANI